Pain Medicine: A Multidisciplinary Approach 9888028162, 9789888028160

Citation preview

Edited by

Siu Lun TSUI, Phoon Ping CHEN, and Kwok Fu Jacobus NG

Pain Medicine

A Multidisciplinary Approach

Pain Medicine

This book is dedicated to all patients with acute, chronic or cancer pain, their families and the health care workers who assist them in the fight against this human suffering

Pain Medicine

A Multidisciplinary Approach

Edited by

Siu Lun TSUI Phoon Ping CHEN Kwok Fu Jacobus NG

Hong Kong University Press 14/F Hing Wai Centre 7 Tin Wan Praya Road Aberdeen Hong Kong © Hong Kong University Press 2010 ISBN 978-988-8028-16-0 All rights reserved. No portion of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage or retrieval system, without prior permission in writing from the publisher.

British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library.

Secure On-line Ordering http://www.hkupress.org

Printed and bound by ColorPrint Production Ltd, Hong Kong, China

Contents Foreword Joseph Chuan Shih YANG

ix

Preface Siu Lun TSUI

xi

Editors, Contributors & Co-contributors

xiii

Section A Scientific Basis of Pain Medicine Chapter 1 Neurobiology and Mechanisms of Pain Michael G. IRWIN, Gordon T.C. WONG

1

Chapter 2 Psychological Concepts of Pain Michael K. NICHOLAS

9

Chapter 3 Principles of Pain Assessment and Evaluation Tools Joanne W.Y. CHUNG

19

Chapter 4 The Clinical Evaluation of Pain Paul J. WRIGLEY, Philip J. SIDDALL

31

Chapter 5 Epidemiology in Chronic Pain, Gender and Cultural Aspects Mary CARDOSA, Phoon Ping CHEN

49

Chapter 6 Biostatistics in Pain Medicine Jacqueline YAP, Tony GIN

63

Chapter 7 Ethics in Pain Medicine Ramani VIJAYAN

81

vi

Contents

Section B Common Clinical Pain Conditions Chapter 8 Acute Pain Management Phoon Ping CHEN, Christopher Ping Wing CHU, Edmond Kin Nam CHUNG

93

Chapter 9 Cancer Pain Siu Lun TSUI, Chi Wai CHEUNG

131

Chapter 10 Headache Chi Tim HUNG, Steven H.S. WONG

157

Chapter 11 Orofacial Pain Chi Tim HUNG, Theresa Tak Lai LI

187

Chapter 12 Neck Pain Ping Hong CHIN

199

Chapter 13 Back Pain Hau Yan KWOK, Kenneth M.C. CHEUNG

207

Chapter 14 Muscular Pain Conditions Milton L. COHEN

221

Chapter 15 Neuropathic Pain Kwok Fu Jacobus NG

235

Chapter 16 Painful Arthritis and Rheumatic Conditions Chak Sing LAU

253

Chapter 17 Pain Associated with Medical Diseases Simon K.C. CHAN, Alice K.Y. MAN

275

Chapter 18 Pain in the Older Person C. Roger GOUCKE

299

Contents

Chapter 19 Pain in Children and Adolescents George CHALKIADIS

vii

311

Section C Pain Pharmacology Chapter 20 Principles of Pharmacological Treatment Carina Ching Fan LI

339

Chapter 21 Opioid Analgesics Ming Chi CHU

347

Chapter 22 NSAIDs, COX-2 Inhibitors and Paracetamol Libby Ha Yun LEE

367

Chapter 23 Antidepressants and Anticonvulsants Philip Wenn Hsin PENG, Geoff Alexander BELLINGHAM

379

Chapter 24 Other Medications and Adjuvants in Pain Management Anne Miu Han CHAN

393

Section D Interventional Procedures in Pain Management Chapter 25 Interventional Procedures in Pain Management: An Overview Steven H.S. WONG

405

Chapter 26 Peripheral Nerve Blocks Theresa Tak Lai LI

419

Chapter 27 The Sympathetic Chain: Efficacy of Sympathetic Blockade and Sympathectomy Philip FINCH

439

Chapter 28 Interventional Procedures for Back and Neck Pain Kai On SUN, Henry Ka Fai TONG

459

viii Contents

Chapter 29 Neuraxial Analgesia Kok Eng KHOR

473

Chapter 30 Spinal Cord Stimulation Tsun Woon LEE

501

Chapter 31 Neurosurgery in Pain Management Kwan Ngai HUNG

511

Section E Multidisciplinary Pain Management Chapter 32 Radiotherapy in the Management of Pain in Cancer Patients Rico K.Y. LIU, Arthur YUE, Gordon K.H. AU

523

Chapter 33 Palliative Care for Patients with Advanced Cancer Rico K.Y. LIU, Raymond S.K. LO

537

Chapter 34 Acupuncture and Traditional Chinese Medicine Anne KWAN

547

Chapter 35 Physiotherapy Anthony W.K. LAU, Leo C.T. CHEUNG

561

Chapter 36 Occupational Therapy for Chronic Pain: Enhancement of the Role of Productivity and Return to Work Chetwyn C. H. CHAN, Connie Y. Y. SUNG

573

Chapter 37 Psychological management in chronic pain Peter W.H. LEE, Amy S.M. FUNG

581

Chapter 38 Functional Rehabilitation and Cognitive Behavioural Interventions Tak Yi CHUI, Michael K. NICHOLAS

599

Index

621

Foreword The world in the 21st century is shaped by technological advances and human demands which inspire new aspirations. People wish not only to live longer but also better, such that the demand for and improvement in their quality of life is more than before a life priority. Pain is at the centre of suffering. For the patient, it becomes an unmitigated evil. For the health care giver, pain relief has been their task since the beginning of time. Yet, the goal of satisfactory pain control at times remains elusive. Pain can be acute or chronic. But unlike most symptoms, the difference between acute and chronic pain is more than just chronological; the mechanisms are also vastly different. Acute pain with its nociceptive function has a physiological meaning. It serves as an alarm or warning system which is fundamental to survival. In this way, pain is rooted in our body’s defence mechanism and intimately relates to other functions, such as those of the autonomic nervous system or gastrointestinal regulation. Chronic pain, on the other hand, often loses its protective function and becomes a disease state. The pain transmission system provides a high capacity for plastic changes, which through the effects of humoral messengers and neural connections affect various organs in different ways. Given the complexity of the extensive mechanisms involved, it is only logical that it is often difficult to deal with pain within any one single medical specialty. The characteristics of pain transmission and the perception systems clearly indicate the need for a holistic approach in treatment. The

human body is too complicated for any individual branch of medicine to master all the information and expertise needed to deal with pain. Doctors are usually trained within set boundaries, and each specialty and discipline will have its own paradigms. Different disciplines will exercise their own ways to influence the specific pain condition. Their knowledge goes to the depth rather than the width of the matter. There is a need to think outside the box to provide the most appropriate and effective treatment. Guidelines to deal with pain need to be established from specialty to specialty. There are also other questions: Can viewpoints about pain differ significantly between various disciplines? How can one exploit treatments offered by those whose training is other than one’s own? Would a more targeted therapy be achieved by referring patients to other specialties? The answers to these problems lie in multidisciplinary pain medicine. They are embedded in this comprehensive book which is edited by Drs. Siu-lun Tsui, Phoon-ping Chen and Kwok-fu Jacobus Ng. Pain Medicine: A Multidisciplinary Approach can be read not only to know more about one’s own specialty, but also to learn how other disciplines deal with the problems of pain. It can thus encourage dialogue between the specialties. While the book is directed toward practitioners managing pain patients, it provides a valuable resource to those in training. It offers all the opportunity to discover new horizons in dealing with the oldest affliction of mankind.

Joseph C.S. Yang MD, Dip Am Board (Anesthesia & Pain Management), FFARCSI, FHKCA, FHKAM, Dip Pain Mgt (HK) Adjunct Professor of Anesthesiology, Columbia University, USA Former Professor and Head, Department of Anaesthesiology, The University of Hong Kong Former Chairman, Pain Management Committee, Hong Kong College of Anaesthesiologists

Preface Pain medicine is now a medical specialty in its own right. Although the multidisciplinary approach is the cornerstone of modern pain medicine, by far the majority of patients with acute, chronic or cancer pain are currently under the care of an individual discipline. Different medical specialists or allied health care teams provide services to pain patients following the approach and traditions of their own discipline. With greater advances in medical science and the growing expectancy of patients, these teams need to work in collaboration to provide good quality care with expertise and complexity. This textbook serves as a platform for different medical specialists and allied health care professionals from which to describe, discuss and share their experience in delivering care to pain patients. Experts in the field of pain medicine from different parts of the world have jointly contributed to the Chapters in this textbook. The Editors would like to express their utmost appreciation for the time and hard work of all contributors and co-contributors who have made this book possible.

The primary aim of this textbook is to serve as a comprehensive basic textbook for pain medicine physicians in their preparation for their higher qualification examination. The book also serves as a reference book for other medical specialists and allied health care professionals who need to take care of patients with acute, chronic or cancer pain. The Chapters are organised into five Sections. The book commences with a Section dedicated to basic science related to pain mechanisms, psychology, assessment, statistical analysis and ethics. This is followed by a Section which contributes to the detailed discussion of different types of clinical pain condition. The other three Sections are dedicated to the different approaches used to manage pain, namely: pharmacological treatment, interventional procedures and other specialised techniques. This book is intended to provide a medium to facilitate and further enhance the quality of our care to the patients who suffer from acute, chronic or cancer pain. We hope that readers will find the book informative and helpful in their clinical practice.

Siu Lun TSUI

Editors, Contributors & Co-contributors EDITORS

Associate Professor Jacobus Kwok Fu NG

Dr. Siu Lun TSUI

MBChB, MD, FANZCA, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt, MBA

MBBS, MD, FFPMANZCA, FANZCA, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt (HKCA)

Consultant Anaesthetist & Head, Division of Pain Medicine, Department of Anaesthesiology, Queen Mary Hospital, Hong Kong SAR Honorary Clinical Associate Professor, Department of Anaesthesiology, The University of Hong Kong Department of Anaesthesiology, Queen Mary Hospital, Room 43, 2/F, F Wing, Main Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected] Dr. Phoon Ping CHEN MBBS, FFPMANZCA, Dip Pain Mgt (HKCA), FHKAM, FHKCA, FANZCA, MHA

Consultant & Chief of Service, Department of Anaesthesiology & Operating Services, Alice Ho Miu Ling Nethersole Hospital & North District Hospital, Hong Kong SAR Honorary Associate Professor, Department Anaesthesia & Intensive Care, The Chinese University of Hong Kong Department of Anaesthesiology & Operating Services, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, Hong Kong SAR [email protected]

Associate Professor, Department of Anaesthesiology and Department of Pharmacology & Pharmacy, The University of Hong Kong, Room 424, Block K, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected]

CONTRIBUTORS & CO-CONTRIBUTORS (in alphabetical order) Dr. Gordon K.H. AU MBBS (London), FRCR, FHKCR, FHKAM

Chief of Service, Department of Clinical Oncology, Queen Mary Hospital, Hong Kong SAR Dr. Geoff Alexander BELLINGHAM MD, FRCPC

Clinical Fellow, Wasser Pain Management Clinic, Mount Sinai Hospital, Toronto, Ontario, Canada Dr. Mary CARDOSA MB, BS, MMed, FANZCA, FFPMANZCA, FAMM

Consultant Anaesthesiologist, Hospital Selayang, Selangor, Malaysia Head of Subspecialty (Pain Medicine), Ministry of Health, Malaysia, 54, Lorong Burhanupdin Helmi 6, Taman Tun Dr. Ismail, 60000 Kuala Lumpur, Malaysia

xiv

Editors, Contributors & Co-contributors

Dr. George CHALKIADIS

Dr. Phoon Ping CHEN

MBBS, DA (Lon), FANZCA, FFPMANZCA

MBBS, FFPMANZCA, Dip Pain Mgt (HKCA), FHKAM, FHKCA, FANZCA, MHA

Staff Anaesthetist and Pain Medicine Specialist, Head, Children’s Pain Management Service, Department of Paediatric Anaesthesia and Pain Management, Royal Children’s Hospital, Flemington Road, Parkville VIC 3052, Australia Clinical Associate Professor, University of Melbourne Murdoch Children’s Research Institute, Australia [email protected] Professor Chetwyn C.H. CHAN PhD

Professor, Applied Cognitive Neuroscience Laboratory, Head, Department of Rehabilitation Sciences, The Hong Kong Polytechnic University Hung Hom, Kowloon, Hong Kong SAR [email protected] Dr. Simon K.C. CHAN MBBS, FANZCA, FHKCA, FHKAM, MHSM, Dip Pain Mgt (HKCA)

Honorary Associate Professor, Consultant Department of Anaesthesia & Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR [email protected] Dr. Anne Miu Han CHAN MBBS, FANZCA, FFPMANZCA, FHKCA, FHKAM, Dip Pain Mgt

Senior Medical Officer, Doctor in Charge of Pain Service, Princess Margaret Hospital Department of Anaesthesia, Princess Margaret Hospital, Lai Chi Kok, Kowloon, Hong Kong SAR [email protected]

Consultant & Chief of Service, Department of Anaesthesiology & Operating Services, Alice Ho Miu Ling Nethersole Hospital & North District Hospital Honorary Associate Professor, Department Anaesthesia & Intensive Care, The Chinese University of Hong Kong Department of Anaesthesiology & Operating Services, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, Hong Kong SAR [email protected] Assistant Professor Chi Wai CHEUNG MBBS, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt (HKCA)

Assistant Professor, Department of Anaesthesiology, The University of Hong Kong Department of Anaesthesiology, The University of Hong Kong, Room 424, Block K, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected] Mr. Leo Chin Ting CHEUNG MSc in Health Care (Physiotherapy), BSc in Physiotherapy, Dip Epidemiology and Biostatistics

Senior Physiotherapist, Department of Physiotherapy, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, Hong Kong SAR [email protected] Professor Kenneth M.C. CHEUNG MBBS, MD, FRCS, FHKCOS, FHKAM (Orth)

Clinical Professor, Deputy Chief, Division of Spine Surgery, LKS Faculty of Medicine, The University of Hong Kong Honorary Consultant Orthopaedic Surgeon, Department of Orthopaedics & Traumatology, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected]

Editors, Contributors & Co-contributors

Dr. Ping Hong CHIN

Professor Joanne W.Y. CHUNG

MB, FHKAM (Orthopaedic Surgery), LMCHK

RN, PhD

Consultant, Department of Orthopaedics & Traumatology, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong SAR

Professor, School of Nursing,The Hong Kong Polytechnic University, Hong Kong SAR [email protected]

Dr. Christopher Ping Wing CHU

Associate Professor Milton L. COHEN

BMedSci, BMBS, FRCP (Canada), FHKAM, FHKCA, MBA

MBBS, MD, FRACP, FAFRM, FFPMANZCA

Senior Medical Officer, Department of Anaesthesiology and Operating Services, Alice Ho Miu Ling Nethersole Hospital & North District Hospital, Hong Kong SAR Dr. Ming Chi CHU MBBS, FHKCA, FANZCA, FFPMANZCA, Dip Pain Mgt (HKCA)

Associate Consultant, Department of Anaesthesia and Intensive Care, Prince of Wales Hospital, Shatin, Hong Kong SAR [email protected]

Consultant Physician, Rheumatology and Pain Medicine, St Vincent’s Campus, Sydney, NSW, Australia Conjoint Associate Professor of Medicine, University of New South Wales St Vincent’s Medical Centre, 376-382 Victoria Street, Darlinghurst NSW 2010, Australia [email protected] Dr. Philip FINCH MBBS, FFARCS, DRCOG, FFPMANZCA, FIPP

Adjunct Professor, Murdoch University Perth Pain Management Centre, PO Box 641, South Perth 6951, Western Australia pfi[email protected]

Dr. Tak Yi CHUI MBBS (HK), MRCP (UK), FRCP (Glasgow), FHKCP, FHKAM (Medicine)

Dr. Amy Shuk-Man FUNG BSocSc, MSocSc, PhD (HK)

Chief of Service (Geriatrics and Rehabilitation), Haven of Hope Hospital, Hong Kong SAR

Head, Hong Kong West Cluster Clinical Psychological Services, Hospital Authority

Physician-in-Charge, Chronic Pain Rehabilitation Programme, Haven of Hope Hospital Haven of Hope Hospital, 8 Haven of Hope Road, Tseung Kwan O, Hong Kong SAR [email protected]

Head & Senior Clinical Psychologist, Department of Clinical Psychology, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected]

Dr. Edmond Kin Nam CHUNG

Professor Tony GIN

MBBS, Dip Pain Mgt (HKCA), FHKCA, FHKAM

MD, FANZCA, FRCA, FHKAM

Formerly Director of Pain Services Department of Anaesthesiology & Operating Services, Alice Ho Miu Ling Nethersole Hospital & North District Hospital, Hong Kong SAR

Chairman and Chief of Service Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR [email protected]

xv

xvi

Editors, Contributors & Co-contributors

Dr. C. Roger GOUCKE

Dr. Anne KWAN

FANZCA, FFPMANZCA, FAChPM (RACP)

MBBS, FANZCA, FFPMANZCA, FHKCA, FHKAM, Dip Pain Mgt, Dip Acup, Dip Epi & Stat, M Pal Care

Clinical Associate Professor, School of Medicine and Pharmacology, University of Western Australia and Head, Department of Pain Management, Sir Charles Gairdner Hospital, Perth WA 6009, Australia [email protected] Dr. Chi Tim HUNG MBBS, FANZCA, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt (HKCA)

Chief of Service and Consultant Anaesthesiologist, United Christian Hospital, Hong Kong Director of Kowloon East Management Centre, Adjunct Associate Professor, The Chinese University of Hong Kong, Department of Anaesthesiology and Pain Medicine, 130 Hip Wo Street, Kwun Tong, Kowloon, Hong Kong SAR [email protected]

Previously Consultant Anaesthetist and Head of Pain Management Team, Queen Elizabeth Hospital

Dr. Hau Yan KWOK

Honorary Clinical Associate Professor, Department of Anaesthesiology, University of Hong Kong, Room 902, S Block, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong SAR [email protected]

Associate Consultant and Honorary Clinical Assistant Professor, The University of Hong Kong The University of Hong Kong Medical Centre, Department of Orthopaedics & Traumatology, Queen Mary Hospital 5/F, Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected]

Dr. Kwan Ngai HUNG MBBS, FRCS (Edin), FCSHK, FHKAM (Surgery)

Consultant and Head, Department of Neurosurgery, Queen Mary Hospital, 701 Administrative Block, 102 Pokfulam Road, Hong Kong SAR [email protected] Professor Michael G. IRWIN MBChB, MD, FRCA, FHKCA, FHKAM (Anaesthesiology), DA

Professor and Head, Department of Anaesthesiology, The University of Hong Kong President, The Hong Kong College of Anaesthesiologists Department of Anaesthesiology, Room 424, Block K, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected] Dr. Kok Eng KHOR MBBS, MMed (Pain Med), Dip Musc Med, FAFMM, FANZCA, FAChPM (RACP), FFPMANZCA

Director of Pain Management, Prince of Wales Hospital, Sydney, Australia [email protected]

MBChB, FHKAM (Orthopaedic Surgery), FHKCOS, FRCSE (Ortho)

Professor Chak Sing LAU MBChB, MD (Hons), FRCP, FHKCA, FHKAM (Internal Medicine)

Chief of Rheumatology, University of Dundee University Division of Medicine & Clinical Therapeutics, Ninewells Hospital and Medical School, Dundee, United Kingdom [email protected] Mr. Anthony Wing Keung LAU PD in Physiotherapy, Post-registration Cert in Spinal Manipulative Therapy, PD in Acupuncture, PD in OSH, MHA, BSc (Econ)

Department Manager, Department of Physiotherapy, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, Hong Kong SAR [email protected]

Editors, Contributors & Co-contributors xvii

Dr. Libby Ha Yun LEE

Dr. Theresa Tak Lai LI

MBBS, FANZCA, FHKCA, FHKAM, Dip Pain Mgt

MBBS, FANZCA, FHKCA, FHKAM, Dip Pain Mgt

Associate Consultant Anaesthetist,

Senior Medical Officer,

Supervisor of Training in Pain Medicine, Queen Mary Hospital, Hong Kong Honorary Clinical Assistant Professor, Department of Anaesthesiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected]

Deputy Team Head, Pain Management Team, Department of Anaesthesiology & OT Services, Queen Elizabeth Hospital 1/F, Block D, 30 Gascoigne Road, Kowloon, Hong Kong SAR [email protected] Dr. Rico K.Y. LIU

Dr. Tsun Woon LEE MBBS, FFARACS, FANZCA, FFPMANZCA, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt

MBBS (Syd), FRCR, FHKCR (Clinical Oncology, Palliative Medicine), FHKAM (Rad), FAChPM, MSocSc (Counselling) (HKU)

Service Director (Clinical & Ambulatory Care), NT West Cluster, Hospital Authority, Hong Kong

Associate Consultant, Department of Clinical Oncology, Queen Mary Hospital,

Hospital Chief Executive, Pok Oi Hospital, Au Tau, Yuen Long, Hong Kong SAR [email protected]

Honorary Clinical Assistant Professor, The University of Hong Kong Department of Clinical Oncology, 1/F, Professorial Block, Queen Mary Hospital, 102 Pokfulam, Hong Kong SAR [email protected]

Professor Peter Wing Ho LEE BSocSc, MSocSc, PhD (HK) Head, Clinical Health Psychology Programme, Department of Psychiatry, The University of Hong Kong Honorary Consultant Clinical Psychologist, Department of Clinical Psychology, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected] Dr. Carina Ching Fan LI MBBS, FANZCA, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt

Pain Management Clinic, Hong Kong Sanatorium & Hospital, 4/F, Central Block, 2 Village Road, Happy Valley, Hong Kong SAR [email protected]

Dr. Raymond S.K. LO MBBS, MD, MHA, Dip Geri Med, Dip Palliat Med, FRCP, FHKAM

Cluster Co-ordinator, Hospice and Palliative Care, New Territories East Cluster Chief of Service, Bradbury Hospice Consultant, Geriatrics and Palliative Medicine, Shatin Hospital and Bradbury Hospice, 17 A Kung Kok Shan Road, Shatin, HONG KONG SAR Dr. Alice K.Y. MAN FANZCA, FHKCA, FHKAM, Diploma in Pain Medicine (HKCA), Dip Pain Mgt, DFM (Monash)

Honorary Assistant Professor, Associate Consultant, Department of Anaesthesia & Intensive Care, Prince of Wales Hospital, Shatin, Hong Kong SAR

xviii Editors, Contributors & Co-contributors

Associate Professor Kwok Fu Jacobus NG

Dr. Kai On SUN

MBChB, MD, FANZCA, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt, MBA

Consultant, Department of Anaesthesia, Kwong Wah Hospital, Kowloon, Hong Kong SAR

Associate Professor, Department of Anaesthesiology and Department of Pharmacology & Pharmacy, The University of Hong Kong, Room 424, Block K, Queen Mary Hospital Authority, 102 Pokfulam Road, Hong Kong SAR [email protected]

Ms. Connie Y.Y. SUNG Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR Dr. Henry Ka Fai TONG

Associate Professor Michael K. NICHOLAS PhD

Director, ADAPT Pain Management Programme Pain Management & Research Centre University of Sydney at Royal North Shore Hospital, St Leonards NSW 2065, Australia [email protected] Associate Professor Philip Wenn Hsin PENG MBBS, FRCPC

Director, Anesthesia Chronic Pain Program, University Health Network and Mount Sinai Hospital Director of Research, Wasser Pain Management Center, Mount Sinai Hospital Associate Professor, Department of Anesthesia, University of Toronto, Toronto Western Hospital, McL 2-405 399 Bathurst Street, Toronto, ON M5T 2S8. [email protected] Associate Professor Philip SIDDALL MBBS, MM (Pain Mgt), PhD, FFPMANZCA

Clinical Associate Professor, Pain Management Research Institute, University of Sydney, Royal North Shore Hospital, Sydney, Australia Pain Management Research Institute, Royal North Shore Hospital, St Leonards, NSW 2065, Australia [email protected]

Associate Consultant, Department of Anaesthesia, Kwong Wah Hospital, Kowloon, Hong Kong SAR Dr. Siu Lun TSUI MBBS, MD, FFPMANZCA, FANZCA, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt (HKCA)

Consultant Anaesthetist & Head, Division of Pain Medicine, Department of Anaesthesiology, Queen Mary Hospital, Hong Kong SAR Honorary Clinical Associate Professor, Department of Anaesthesiology, The University of Hong Kong Department of Anaesthesiology, Queen Mary Hospital, Room 43, 2/F, F Wing, Main Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR [email protected] Professor Ramani VIJAYAN MBBS, DA (Lon), FFARCS (I), FFARCS (Eng), FRCA, FANZCA, FAMM

Professor, Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia President, Malaysian Association for the Study of Pain Department of Anaesthesiology, University of Malaya, 50603 Kuala Lumpur, Malaysia [email protected]

Editors, Contributors & Co-contributors

xix

Assistant Professor Gordon T.C. WONG

Dr. Paul WRIGLEY

MBBS, BSc (Med), FANZCA, FHKCA, FHKAM (Anaesthesiology)

MBBS, MM (Pain Mgt), PhD, FANZCA, FFPMANZCA

Department of Anaesthesiology, The University of Hong Kong, Room 424, Block K, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR Dr. Steven H.S. WONG MBBS, FANZCA, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt

Senior Lecturer, Senior Staff Specialist in pain medicine Pain Management Research Institute, Division of the Kolling Institute, University of Sydney, Royal North Shore Hospital, St Leonards, NSW, Australia 2065 [email protected]

Consultant Anaesthetist, Head of Pain Management Team, Department of Anaesthesiolgy, Queen Elizabeth Hospital

Dr. Jacqueline YAP

Honorary Clinical Associate Professor, Faculty of Medicine, The University of Hong Kong

Consultant, Department Anaesthesia, Caritas Medical Centre, Hong Kong SAR [email protected]

President, The Society of Anaesthetists of Hong Kong Department of Anaesthesiology, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong SAR [email protected]

MBBS, FANZCA, FFPMANZCA, FHKCA, FHKAM (Anaesthesiology), Dip Pain Mgt, MSc (Epidemiology & Biostatistics), MHSM

Dr. Arthur YUE MBBS

Medical Officer, Department of Clinical Oncology, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR

1

Michael G. IRWIN, Gordon T.C. WONG

Neurobiology and Mechanisms of Pain

Introduction

INTRODUCTION AT THE PERIPHERY Nociceptors: types, location and function The inflammatory milieu Pathway to the central nervous system SPINAL CORD PAIN AND MEMORY BRAIN CONCLUSION REFERENCES

A thorough understanding of the mechanisms and neurobiology of pain is important for both effective utilisation of current drug regimes and for the future development of new therapeutic targets. Pain is a net result of peripheral and central neuronal sensitisation and a balance between excitatory and inhibitory function at different levels within the nervous system. Peripheral tissue damage and trauma release neurotransmitters and result in increased local concentrations of arachidonic acid metabolites, including prostaglandins and leukotrienes. In addition to directly activating peripheral sensory nerve fibres, these agents can trigger degranulation of nearby mast cells and sensitise the peripheral nerve terminal to subsequent stimuli. Activation of these nerves will result in the generation of impulses that travel up sensory nerve fibres and synapse in the dorsal horn of the spinal cord. The transmitted impulses will then undergo further modulation before transmission via the thalamus to the cortex where they are perceived as pain (Fig. 1.01). Persistent nociceptive stimuli and inflammation can lead to a number of structural and functional changes along the nerve pathway. Such plasticity of the nervous system may increase the frequency and intensity of the action potentials propagated proximally along a nerve fibre, thus amplifying the pain signal to the central nervous system (CNS). Anatomical and chemical changes such as increased substance P and glutamate concentrations occur in the dorsal root ganglia (DRG), causing proliferation and the sprouting of terminals into different laminae of the DRG [25]. Glutamate activates spinal cord amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors [23]. Increased sensitivity and responsiveness of central pain-signalling neurons causes increased expression of cyclo-oxygenase-2 (COX-2) in the spinal cord [43,44]. This mechanism produces

2

Michael G. IRWIN, Gordon T.C. WONG

Figure 1.01

Diagram showing some of the important components of the pain pathway.

prostaglandins in the CNS influencing central pain sensitisation. It is becoming apparent that poorly controlled pain initiates changes in both peripheral and CNSs through inflammation, neuronal

hyperexcitability and synaptic function alteration. This can lead to persistence and amplification of pain and possibly even the development of chronic pain states.

Neurobiology and Mechanisms of Pain

At the Periphery Nociceptors: types, location and function Nociceptors are sensory receptors that generate the signals that cause the perception of pain (nociception). The receptors are usually activated in response to tissue injury but these nerve endings may also be responsible for persistent pain. One type of such pain state termed neuropathic pain can occur sometime after the resolution of peripheral tissue damage or inflammation. Neuropathic pain almost invariably involves lesions of a part of the nociceptive pathway. Hyperalgesia relates to the acquisition of transduction capacity for stimuli that ordinarily do not activate nociceptors. There are two ways that nociceptors may be sensitised. One is for the transduction channel to sensitise (i.e. a bigger generator potential occurring from a given natural stimulus). The other mechanism is a decrease in threshold of the sodium channels responsible for spike initiation [22].

3

Nociceptors are ubiquitous throughout the body and can be found in external tissues such as skin, cornea and mucosa and certain internal organs such as muscle, joint, bladder and gut. The cell bodies of these neurons are located in either the dorsal root ganglia or the trigeminal ganglia. There are several types of nociceptors and they are classified according to the stimulus modalities to which they respond, i.e. thermal, mechanical or chemical. They transduce a variety of stimuli into receptor action potentials, which in turn trigger action potentials along the afferent nerve fibre. Some nociceptors respond to more than one of these modalities and are, consequently, designated polymodal. Others respond to none of these modalities and are referred to as sleeping or silent nociceptors. Estimates are that up to 40% of C and 30% of A-delta fibres are silent nociceptors [27]. These receptors may become sensitised to certain physiological or chemospecific stimuli under inflammatory conditions. Thermal nociceptors are activated by noxious heat or cold, temperatures above 45°C and below 5°C [7].

Figure 1.02 The inflammatory milieu. K+ = potassium; AA = arachidonic acid; NorAd = noradrenaline; COX = cyclo-oxygenase; PGs = prostaglandins; LT = leukotriene; ILs = interleukins; NGF = nerve growth factor; 5-HT = 5-hydroxytryptamine; SP = substance P; H+ = protons.

4

Michael G. IRWIN, Gordon T.C. WONG

Mechanical nociceptors respond to excess pressure or mechanical deformation. Polymodal nociceptors respond to damaging stimuli of a chemical, thermal or mechanical nature. Primary afferent nerve fibres transduce different forms of energy into generator potentials. If of sufficient magnitude, these generator potentials lead to action potentials. The action potentials propagate along the axon to the spinal cord.

The inflammatory milieu Intense pressure can cause cell damage and release of arachidonic acid, potassium and hydrogen. This will induce production of cyclo-oxygenase enzyme in the peripheral tissue, which causes an increased synthesis of prostaglandins from arachidonic acid [37]. Arachidonic acid is also the precursor for other prostanoids such as leukotrienes and hydroxyacids. Besides triggering an inflammatory cascade response, prostanoids also activate nociceptors, increase their responsiveness to other stimuli and start off the pain transmission [20]. During inflammation, noradrenaline is released from the sympathetic efferent fibres, which will also stimulate the nociceptors. Other inflammatory mediators, such as interleukins, are known to have a direct stimulating effect on nociceptors [12]. Kinins are structurally related polypeptides, such as bradykinin and kallikrein. They are members of the autacoid family and have proinflammatory effects such as release of cytokines and free radicals and stimulate sympathetic neurons to contract vascular endothelial cells [10]. They also induce histamine release from mast cells, serotonin (5-HT) from platelets and mast cells and neuropeptides like substance P from damaged tissue (axon reflex). They trigger significant vasodilatation and neurogenic oedema. Following the release of these algogenic chemical injury products, previously silent receptors are activated by a wide range of thermal and mechanical stimuli and may also develop a background discharge [35]. The expression of nerve growth factor (NGF) is high in injured and inflamed tissues, and activation of the NGF receptor tyrosine kinase TrkA on nociceptive neurons triggers and potentiates pain signalling [1]. Sprouting of epidermal nerve fibres is initiated by increased NGF and is found in combination with localised pain and hyperalgesia [36]. This also occurs in pruritic lesions, suggesting that similar mechanisms of neuronal sprouting

and sensitisation exist for both pain and pruritus on a peripheral level [32]. Consequently, antiNGF has the potential to be a novel class of analgesic [14]. Nerve growth factor is known to up-regulate neuropeptides, especially substance P and calcitonin-gene-related peptide [39]. Although substance P has been found to have an important role in the induction of pain and hyperalgesia, there is little evidence for the clinical analgesic efficacy of antagonists of its receptor, the neurokinin 1 (NK1) receptor [15]. Low pH also activates several ion channels to transduce pain, i.e. acid-sensing ion channels, vanilloid receptors, purinergic receptors and potassium channels. This may be important in ischaemia-induced pain [41]. Important ion channels in pain include the following. Transient receptor potential vanilloid (TRPV) channels are phosphorylated and up-regulated by tissue injury and inflammation [29]. Ankyrin-repeat TRP 1 (TRPA1) channels in peripheral nociceptors can be opened with pungent chemicals (e.g. mustard, tear gas) and high threshold mechanical stimuli [4]. P2X are purinergic receptors that are activated by adenosine triphosphate, elevated levels of which are found in inflamed tissues. P2X receptors are also found in the dorsal root ganglion neurons and may play a role in the development of neuropathic pain after nerve injury [24].

Pathway to the Central nervous system Nociceptors may have either A-delta fibre axons (transmit signals at 20 m/s) or more slowly conducting C fibre axons (2 m/s). Thus, pain often comes in two phases. The first is mediated by the fast-conducting A-delta fibres responding either to dangerously intense mechanical or to mechanothermal stimuli, which have receptive fields that consist of clusters of sensitive spots. The unmyelinated C fibres conduct to thermal, mechanical and chemical stimuli, which is why their nociceptors are referred to as polymodal. Together these nociceptors allow the person to feel pain in response to damaging pressure, excessive heat, excessive cold and a range of chemicals, the majority of which are damaging to the tissue surrounding the nociceptor. Afferent nociceptive fibres travel back to the spinal cord where they form synapses in its dorsal horn.

Neurobiology and Mechanisms of Pain

Spinal Cord The dorsal horn of the spinal cord is the pivotal gateway for pain transmission to the CNS. When the action potentials from A-delta or C fibres reach the central terminals of sensory neurons in the spinal cord, calcium influx through presynaptic voltage-gated calcium channels triggers the release of pronociceptive neurotransmitters and neuromodulators, which excite or sensitise secondary neurons in the superficial lamina of the dorsal horn. The cells in the dorsal horn are divided into physiologically but not anatomically distinct layers called laminae and the various types of fibre form synapses in different layers. There is a degree of overlap between these laminae, with each lamina containing more than one type of neuron. A-delta fibres form synapses in laminae I, II and V; C fibres connect with neurons in lamina I and II; and A-beta fibres connect with lamina IV. Postsynaptic fibres converge in lamina V where wide dynamic range neurons are present. Wide dynamic range neurons are those that receive input from both noxious and non-noxious stimuli. They can increase their firing rate in response to increasing levels of stimulation (graded response); the high threshold neurons are those that are activated only by noxious stimulation, and low threshold neurons are only activated by non-noxious stimulation. Central terminals of primary afferents release excitatory amino acids such as aspartate, glutamate and neurokinins (e.g. substance P), which activate receptors on the postsynaptic cells. Activation of AMPA and NK1 receptors leads to priming of the NMDA receptor complex. Glutamate release results in further activation with removal of a magnesium “plug” from the NMDA receptor and subsequent calcium influx. The interaction of these three receptors is thought to play an important role in the pathophysiology of persistent pain states [28]. Calcitonin-gene-related peptide is released from high threshold fibres along with substance P and can expand the spinal cord area from which substance P is released, thereby further increasing excitability. Substance P itself can also increase the release of excitatory amino acids enhancing the responses of dorsal horn neurons to glutamate or NMDA. As a result, neuropeptide antagonists may have therapeutic potential in preventing central sensitisation [2].

5

Intracellular calcium influx to the NMDA receptor acts on a calmodulin sensitive site and activates the enzymes nitric oxide synthase and cyclo-oxygenase2 (COX-2). Excessive production of nitric oxide and prostaglandin plays major roles in neural and glial excitation and central sensitisation. Neurochemical changes result in several plasticity responses including apoptosis (glial and neuronal cell death), axonal sprouting and new afferent connections. Normally, A-beta fibre stimulation by innocuous stimuli is unable to activate dorsal horn cells. As a result of central sensitisation, however, A-beta fibre input becomes sufficient and low-threshold stimuli now produce painful responses. These anatomical changes underlie the development of long term potentiation and chronic pain [17]. Synaptic transmission between the primary afferent nociceptors and the dorsal horn neurons can be modified by a number of mechanisms, e.g. repetitive stimulation from the periphery can amplify or prolong the response to noxious input. This usedependent synaptic plasticity has been described as “wind up” [26]. Wind up is dependent on NMDA and neurokinin receptor activation [38] and is a separate phenomenon to central sensitisation, which is an increased excitability of neurons within the spinal cord with an expansion in receptive field, reduction in threshold and the recruitment of novel inputs. Clinically, central sensitisation results in secondary hyperalgesia, allodynia and pain generation by activating A-beta mechanoreceptors and signal transduction pathways. It has been suggested that wind up initiates and maintains central sensitisation [38]. Central sensitisation results in hyperalgesia and two types of mechanical hyperalgesia can be differentiated. In allodynia, touch that is normally painless can trigger painful sensations (touch- or brush-evoked hyperalgesia). Although this sensation is mediated by myelinated mechanoreceptor units, it requires the ongoing activity of primary afferent C-nociceptors. The second type of mechanical hyperalgesia results in slightly painful pin prick stimulation being perceived as more painful. This type has been called punctate hyperalgesia and does not require ongoing activity of primary nociceptors for its maintenance. Administration of cyclooxygenase inhibitors reduces the development of hyperalgesia and allodynia [18].

6

Michael G. IRWIN, Gordon T.C. WONG

Types of hyperalgesia Touch- or brush-evoked hyperalgesia Punctate hyperalgesia

Other receptors that are present in the dorsal horn and are known to have moderating effects on neurotransmission include alpha-2-adrenoceptors (subtype A) and opioid receptors. Descending noradrenergic inhibitory pathways modulate nociceptive transmission and spinal sensitisation after tissue injury. Spinal alpha-2-adrenoceptor agonists as well as noradrenaline transporter inhibitors relieve mechanical hyperalgesia [30] and alpha-2-activation also depresses nerve fibre action potentials, especially in the small unmyelinated C fibres [13]. Calcium channel auxiliary subunit alpha-2-delta-1 also plays an important role in neuropathic pain processing as it is up-regulated in the DRG after spinal nerve injury. Intrathecal alpha-2-delta-1 antisense oligonucleotides block injury-induced dorsal horn alpha-2-delta-1 subunit up-regulation and diminish tactile allodynia in rats [21]. Pregabalin, used in the treatment of neuropathic pain and anxiety disorders, binds specifically to the alpha-2-delta-1subunit of voltagedependent Ca2+ channels with a high affinity and reduces calcium current [5]. Activation of opioid receptors reduces neuronal excitability through the inhibition of voltage-dependent Ca2+ channels and adenylyl cyclase, and opening of K+ channels, and this opioid induced reduction in excitability will lead to an inhibition of pain [34]. Adenosine triphosphate sensitive potassium (KATP) channels are opened and modulated by both opioid and non-opioid G-protein coupled receptors to also produce antinociception [42]. There is evidence that activation of central sensitisation and pain is also mediated via humoral messengers. Although it was thought that peripheral cytokines could not cross the blood-brain barrier, it has now been demonstrated that cerebral vascular cells that form the blood-brain barrier express components that enable a blood-borne cytokine to stimulate the production of prostaglandin E2, an inflammatory mediator and powerful modulator of nociception [11]. These cells have, on their surface, receptors that specifically recognise interleukin (IL)-1-beta indicating that the activated immune system controls central reactions to peripheral inflammation through a prostaglandindependent, blood-borne cytokine-mediated pathway. Interestingly, it is mainly the increase

in cerebrospinal levels of IL-1-beta that mediates local inflammation in the brain and not the sensory inflow from nerve fibres, which is thought to be mainly important for the widespread induction of COX-2 expression in the CNS leading to the release of prostanoids and resulting in pain [33]. It has also been shown that high concentrations of proinflammatory cytokines (IL-1-beta, IL-2, IL-6, IFN-gamma, tumour necrosis factor [TNF]alpha) in the plasma correlate with increasing pain intensity. Chronic pain patients also show a significant increase in plasma levels of nitric oxide in comparison to healthy controls [16].

Pain and Memory The prolonged changes in sensitivity observed during central sensitisation are similar to the synaptic changes required for learning and memory. The NMDA-dependent long term potentiation (LTP) within the hippocampus appears to be integral in the cellular mechanisms of memory as this is the principal cellular mechanism thought to underlie neuronal plasticity [31]. A recent report has provided data in humans that pain and memory have very similar mechanisms and that LTP in nociceptive pathways enhances human pain sensitivity via interaction of two afferent pathways [19]. It has been suggested that, consequently, it may be difficult to develop treatments that only affect pain without influencing memory [8].

Brain Information is sent from the spinal cord to the thalamus and the cerebral cortex in the brain. The receptive fields of all pain-sensitive neurons are relatively large, particularly at the level of the thalamus and cortex, presumably because the detection of pain is more important than its precise localisation. Pain is a complex experience consisting of sensory discriminative, affective, cognitive and motivational components. Brain imaging studies have significantly widened our knowledge and understanding of the complexity of pain presentation by attempting to correlate different aspects of the pain sensation to particular brain areas. It is generally accepted that spatial, temporal and intensity aspects of pain perception are processed in the primary

Neurobiology and Mechanisms of Pain

and secondary somatosensory cortex (S1 and S2 respectively), whereas the anterior cingulate cortex and insular cortex are involved in the affectivemotivational component [40]. Somatotropic representation of pain is reported for the S1, but might be much clearer in the dorsal posterior insula [3]. This would confirm a different central projection pathway for pain primary projections to the dorsal posterior insula. This part of the brain may function as a basic interoceptive cortex with homeostatic functions [6].

by the biochemical makeup of their immediate environment. Such plasticity in the system is responsible for the development of abnormal and chronic pain states, well beyond the duration of the inciting injury. Understanding of the neurobiology behind pain transmission is pivotal in the effective use of available analgesics and for the development of future therapy.

Key points •

Conclusion The body of knowledge regarding nociception continues to grow as techniques in characterising receptors and neurotransmitters continue to improve. The transmission of a pain signal from the periphery to the brain involves complex interactions between different types of neurons, through release of various neurotransmitters and receptor and ion channel activation. The perception of pain is also affected by descending influences from the brain. The components of the “pain pathway” have potential for modification both in terms of structure and function. Changes in the neuronal makeup are largely influenced

7

• • •

•

•

Pain perception is the net result of ascending and descending excitatory and inhibitory influences Anatomical and biochemical changes can alter nociception anywhere along the pain pathway Nociceptors are ubiquitous throughout the body and may be mono- or polymodal Peripheral tissue damage and/or inflammation increases the local concentration of mediators that activate and up-regulate nociceptors and ion channels The dorsal horn of the spinal cord is an important target for pain modulation as primary afferent fibres from peripheral nociceptors synapse here Central sensitisation can result in mechanical hyperalgesia.

References Allen SJ, Dawbarn D. Clinical relevance of the neurotrophins and their receptors. Clin Sci 2006;110:175–91. Ambalavanar R, Moritani M, Moutanni A, et al. Deep tissue inflammation up-regulates neuropeptides and evokes nociceptive behaviors which are modulated by a neuropeptide antagonist. Pain 2006;120:53–68. 3. Apkarian AV, Bushnell MC, Treede RD, et al. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005;9:463–84. 4. Bautista DM, Jordt SE, Nikai T, et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 2006;124:1269–82. 5. Bian F, Li Z, Offord J, et al. Calcium channel alpha2-delta type 1 subunit is the major binding protein for pregabalin in neocortex, hippocampus, amygdala, and spinal cord: An ex vivo autoradiographic study in alpha2-delta type 1 genetically modified mice. Brain Res 2006;1075:68–80. 6. Brooks J, Tracey I. From nociception to pain perception: Imaging the spinal and supraspinal pathways. J Anat 2005;207:19–33. 7. Caterina MJ, Rosen TA, Tominaga M, et al. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 1999;398:436–41. 8. Coyle DE. Spinal mechanisms of pain. Int Anesthesiol Clin 2007;45:83–94. 9. Craig AD. A new view of pain as a homeostatic emotion. Trends Neurosci 2003;26:303–7. 10. Dray A. Inflammatory mediators of pain. Br J Anaesth 1995;75:125–31. 11. Ek M, Engblom D, Saha S, et al. Inflammatory response: Pathway across the blood-brain barrier. Nature 2001;410:430–1. 1. 2.

8

Michael G. IRWIN, Gordon T.C. WONG

12. Ferreira SH. The role of interleukins and nitric oxide in the mediation of inflammatory pain and its control by peripheral analgesics. Drugs 1993;46(Suppl 1):1–9. 13. Gaumann DM, Brunet PC, Jirounek P. Clonidine enhances the effects of lidocaine on C-fiber action potential. Anesth Analg 1992;74:719–25. 14. Hefti FF, Rosenthal A, Walicke PA, et al. Novel class of pain drugs based on antagonism of NGF. Trends Pharmacol Sci 2006;27:85–91. 15. Hill R. NK1 (substance P) receptor antagonists — why are they not analgesic in humans? Trends Pharmacol Sci 2000;21:244–6. 16. Koch A, Zacharowski K, Boehm O, et al. Nitric oxide and proinflammatory cytokines correlate with pain intensity in chronic pain patients. Inflamm Res 2007;56:32–7. 17. Koltzenburg M. Neural mechanisms of cutaneous nociceptive pain. Clin J Pain 2000;16:S131–8. 18. Koppert W, Wehrfritz A, Korber N, et al. The cyclo-oxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans. Pain 2004;108:148–53. 19. Lang S, Klein T, Magerl W, et al. Modality-specific sensory changes in humans after the induction of long-term potentiation (LTP) in cutaneous nociceptive pathways. Pain 2007;128:254–63. 20. Levine JD, Fields HL, Basbaum AI. Peptides and the primary afferent nociceptor. J Neurosci 1993;13:2273–86. 21. Li CY, Song YH, Higuera ES, et al. Spinal dorsal horn calcium channel 2delta-1 subunit up-regulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci 2004;24:8494–9. 22. Magerl W, Fuchs PN, Meyer RA, et al. Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia. Brain 2001;124:1754–64. 23. Malmberg AB, Yaksh TL. Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Science 1992;257:1276–9. 24. McGaraughty S, Chu KL, Namovic MT, et al. P2X(7)-related modulation of pathological nociception in rats. Neuroscience 2007;146:1817–28. 25. McMahon SB, Cafferty WB, Marchand F. Immune and glial cell factors as pain mediators and modulators. Exp Neurol 2005;192:444–62. 26. Mendell LM, Wall PD. Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres. Nature 1965;206:97–9. 27. Michaelis M, Habler HJ, Jaenig W. Silent afferents: A separate class of primary afferents? Clin Exp Pharmacol Physiol 1996;23:99–105. 28. Nishiyama T, Yaksh TL, Weber E. Effects of intrathecal NMDA and non-NMDA antagonists on acute thermal nociception and their interaction with morphine. Anesthesiology 1998;89:715–22. 29. Numazaki M, Tominaga M. Nociception and TRP channels. Curr Drug Targets CNS Neurol Disord 2004;3:479–85. 30. Obata H, Conklin D, Eisenach JC. Spinal noradrenaline transporter inhibition by reboxetine and Xen2174 reduces tactile hypersensitivity after surgery in rats. Pain 2005;113:271–6. 31. Pastalkova E, Serrano P, Pinkhasova D, et al. Storage of spatial information by the maintenance mechanism of LTP. Science 2006;313:1141–4. 32. Roosterman D, Goerge T, Schneider SW, et al. Neuronal control of skin function: The skin as a neuroimmunoendocrine organ. Physiol Rev 2006;86:1309–79. 33. Samad TA, Moore KA, Sapirstein A, et al. Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 2001;410:471–5. 34. Satoh M, Minami M. Molecular pharmacology of the opioid receptors. Pharmacol Ther 1995;68:343–64. 35. Schmidt R, Schmelz M, Torebjork HE, et al. Mechano-insensitive nociceptors encode pain evoked by tonic pressure to human skin. Neuroscience 2000;98:793–800. 36. Sivilia S, Paradisi M, D’Intino G, et al. Skin homeostasis during inflammation: A role for nerve growth factor. Histol Histopathol 2008;23:1–10. 37. Smith WL, DeWitt DL, Garavito RM. Cyclo-oxygenases: Structural, cellular, and molecular biology. Annu Rev Biochem 2000;69:145–82. 38. Urban L, Thompson SW, Dray A. Modulation of spinal excitability: Co-operation between neurokinin and excitatory amino acid neurotransmitters. Trends Neurosci 1994;17:432–8. 39. Verge VM, Richardson PM, Wiesenfeld-Hallin Z, et al. Differential influence of nerve growth factor on neuropeptide expression in vivo: A novel role in peptide suppression in adult sensory neurons. J Neurosci 1995;15:2081–96. 40. Vogt BA. Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci 2005;6:533–44. 41. Woo YC, Park SS, Subieta AR, et al. Changes in tissue pH and temperature after incision indicate acidosis may contribute to postoperative pain. Anesthesiology 2004;101:468–75. 42. Wood JN. Ion channels in analgesia research. Handb Exp Pharmacol 2007;177:329–58. 43. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science 2000;288:1765–9. 44. Yaksh TL, Dirig DM, Malmberg AB. Mechanism of action of nonsteroidal anti-inflammatory drugs. Cancer Invest 1998;16:509–27.

2

Michael K. NICHOLAS

Psychological Concepts of Pain

Introduction The conceptualisation of pain has clear significance for its explanation, assessment and treatment. Throughout recorded history ideas about the nature of pain have fluctuated and even today multiple views are held. This chapter attempts to critically review the different concepts of pain that exist today and their implications for assessment and treatment. This understanding should provide the reader with a perspective from which to make sense of the different assessment and treatment modalities, whether they are physical, psychological and/or social.

Definitions of Pain INTRODUCTION DEFINITIONS OF PAIN HISTORICAL PERSPECTIVES PAIN AS A SENSATION OR EMOTION? MODERN PERSPECTIVES BIOPSYCHOSOCIAL MODELS OF PAIN PAIN AS A RESPONSE RATHER THAN A SENSATION? CLINICAL IMPLICATIONS

While most people would agree with Kleinman’s [38] observation that pain is a ubiquitous human experience, agreement on definitions of pain has proved more elusive. At the lay level, pain might be defined as that which hurts. Unfortunately, this has a circular aspect: what hurts is pain. Not surprisingly, the definition of pain (as well as its explanation and treatment) has always depended on the perspective or framework from which it is viewed [25]. Although a comprehensive review of the history of pain is beyond the scope of this chapter (see Bonica and Loeser [12]), some coverage of the major concepts of pain through history should help to provide a useful perspective for understanding the current debates on the nature of pain. A key debate over definitions of pain has centred around questions of whether it is a sensation, like smell, or something more complex, like a need state [66] or an emotional experience, or even a type of response. Wall [66], for example, wrote: Pain is better defined as an awareness of a need state rather than a sensation. It serves more to promote healing

10

Michael K. NICHOLAS

than to avoid injury. It has more in common with the phenomenon of hunger and thirst than with seeing or hearing. The period after injury is divided into the immediate, acute and chronic stages. In each stage it is shown that pain has only weak connection to injury but a strong connection to the body state. However, around the same time Mountcastle [48] described pain as “that sensory experience evoked by stimuli that injure or threaten to destroy tissue. Defined introspectively by every man as that which hurts.” Not surprisingly, these different perspectives on pain have extensive historical roots.

Historical Perspectives The great Roman physician Galen (AD 131–200) considered that pain was a sensation and, like other sensations, was centred in the brain. Similarly, in ancient Egypt pain was also considered to be a sensation, but one that arose from wounds and from internal afflictions. In this view, pain was regarded as a sensation experienced in the heart, and bodily injuries were thought to communicate painful sensations to the heart via a network of vessels. However, Egyptians also believed that pain could arise from the invasion of the body by evil spirits that entered via different orifices during the night; the obvious way of dealing with these spirits was to eject them from the body by sneezing, sweating, vomiting or urinating. In ancient Greece, while Aristotle (384–322 BC) also considered pain to be felt in the heart. He differentiated it from the five senses, describing it as a quality or passion of the soul, a feeling that was the opposite of pleasure (as Plato had previously noted when pain was relieved it was followed by pleasure). Bonica and Loeser [12] noted that this view of pain as an emotional construct, a passion of the soul, held considerable influence for the next 2,000 years, at least in Europe. Through that time, however, the brain came to be seen as a site of all senses, and pain. Even so, the question of whether pain was a sensation or emotional experience continued to be debated. The idea that pain was an emotional experience was also popular in the Vedas and the Upanishads

of ancient India. These texts suggested that the frustration of desires sets the scene for pain experiences. Thus, the intervention should derive from identification of the frustrated desire, which may then be addressed. Like the Europeans at around the same period, the authors of these books also considered that the heart was the anatomical seat of emotional experience, whether of joy or pain. Between the eighth and the fifth centuries BC, practitioners of traditional Chinese medicine developed the view that the vital energy of the body, called chi, circulates to all parts of the body via a network of 14 channels or meridians, each serving an important organ system or function. In the healthy state, the two opposing life forces (yin and yang) were thought to be in balance and assisted the circulation of chi within the body. Disease and pain were attributed to obstructions (deficiency) or outpourings (excess) in the circulation of chi, which, in turn, created an imbalance in yin and yang. Acupuncture therapy was intended to correct this imbalance and resolve disease and pain. Thus, in this view, pain was a symptom or indication of an imbalance between the opposing life forces within the body. The practice of exercises like t’ai chi was also thought (and still is) to be a way of restoring the balance between yin and yang.

Pain as A Sensation or Emotion? In English, the word pain is derived from the Latin word poena, meaning “punishment”. This is linked to the idea that pain was attributable not to demons or excess vital heat, but rather a sin committed by the pain sufferer and possibly relievable by prayer or some type of appeasement of the relevant deity. It is not difficult to see how pain, sin and punishment have been linked in (especially religious) writings and practices, over many centuries. The persistence of the view that pain is an experience with strong emotional features, inextricably linked to meaning, is matched by the persistence of sensory theories of pain. The sensory theory of pain received more support in the 19th and 20th centuries as the physiology of the nervous system was increasingly described and studied. Terms like “pain nerves” appeared as a means of linking the experience of

Psychological Concepts of Pain

11

pain to particular nerve pathways based on the research of people like Müller and Von Frey. Von Frey considered there were four main cutaneous senses: touch, warmth, cold and pain, each with its own special projection system or pathway to a brain centre responsible for that sensation. Von Frey also designated free nerve endings in the body as pain receptors. From this perspective an intervention that blocked or destroyed a “pain nerve” might be expected to relieve all pain, but as has been noted for some time this is not always successful [41].

if they don’t report it. In other words, these models appear to imply that it is possible to have pain without knowing it. From this perspective also, the corollary that a person cannot have pain if there is no obvious stimulus must also be true. However, as many clinicians and researchers have noted, these conclusions are doubtful and inconsistent with many clinical observations [67]. More recent reviews have confirmed the variable nature of the relationship between pain experience and noxious stimuli [3, 18, 27].

The approach to explaining the neural basis of pain as a separate sensation ultimately led to what has been described as the “specificity theory” of pain. This theory was opposed by those who argued that pain and other sensations, like touch and temperature, were not separate sensations, but rather pain was the result of excessive stimulation of the fibres underlying the other sensations. This “intensive (later called “central summation”) theory” was an elaboration of aspects of Aristotle’s model by people like Darwin, Erb and Goldsheider. Essentially, this theory stated that pain could be experienced when stimulation of a sensory system reached a critical level.

The idea that pain must be related to a stimulus can also be seen in a number of early (and even some more recent) psychiatric and medico-legal texts. For example, notions that pain can be divided into summary categories, such as either “organic” or “psychological” appear in earlier versions of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM). In DSM-III [1], the diagnosis of Psychogenic Pain Disorder was described and central to this diagnosis were the implicit assumptions that the cause of all pain syndromes is known, as well as an implicit acceptance of a unidimensional model of pain: namely that pain is either physical or psychogenic (see Turk and Rudy [59] for more discussion of this).

Despite their differences, both the specificity and intensive/summation theories of pain shared the view that pain was primarily a sensation. Philosophically, these sensory theories of pain (developed during the 19th and 20th centuries) are generally believed to have drawn on the writings of Descartes in the 17th century. Descartes wrote of people being composed of a soul and a body and considered that the body was “nothing but a statue or machine” (from a translation of Descartes’ work by Cottingham et al. [16]). In this dualistic model of mankind (with its separation between mind and body), although pain was perceived by the mind (soul), Descartes indicated that pain could be fully explained by describing the bodily mechanism that produced it [5]. This approach, now often described as a reductionistic view [38], has continued to play a central role in the debate over definitions and explanations of pain. One feature of these sensory models and their underlying mind-body separation is that they are reliant on defining pain in terms of a stimulus (e.g. injury or tissue damage). One implication of this is that if a person is injured they must have pain, even

The more recent version of this manual (DSM-IV [2]) has dropped the term “psychogenic” in favour of just Pain Disorder. The criteria for the diagnosis are that A) the pain must involve one or more anatomical sites and be the predominant focus of the clinical presentation; B) the pain must cause clinically significant distress and impairment in important areas of functioning, such as occupation and social activities; and C) psychological factors must play an important role in the onset, severity, exacerbation or maintenance of the pain. Three subtypes of the disorder were identified according to the assessed nature and degree of their association with psychological factors. While mental health professionals have generally regarded the more operational approach of DSM-IV as an improvement over the earlier DSM versions, criticisms of its handling of pain have remained. Fishbain [25], for example, concluded that the pain disorder category “has little utility for the pain clinician”. Fishbain pointed out that the diagnosis is over-inclusive (almost all patients attending a pain clinic would meet the criteria), and that criterion C not only requires a value judgement by

12

Michael K. NICHOLAS

the clinician but the assessment of the relationships between pain report, psychological variables and medical status is of doubtful validity. Nevertheless, it should also be recognised that the DSM-IV did acknowledge that psychological factors could play a number of possible roles in the experience of pain, in addition to organic factors, and this idea will be explored later in this chapter. A modern version of pain as an emotion might be seen in the work of those who have promoted the idea of chronic pain being conceptualised as a type of depression (e.g. “masked depression” [7]), especially when no clear organic basis can be found for the pain. While there is a significant overlap of the clinical signs and symptoms of depression and chronic pain (e.g. sleep disturbance, concentration difficulties and anhedonia), theories that chronic pain is a type of depression have not been validated in the research literature. Instead, the weight of evidence supports the view that depression is more likely to be a consequence of chronic pain than the reverse [26, 31]. However, chronic pain patients who have a comorbid mental disorder (such as depression) tend to have a more impaired quality of life than when there is no comorbidity [4]. Also, treatment outcomes can be compromised when both pain and a mental disorder are present but only one of them is targeted for treatment. For example, higher levels of depression are related to poorer treatment outcomes for chronic pain patients [14, 37], as well as higher health care costs over time [23]. In addition, the presence of pain in those who are being treated for mood disturbance has been found to interfere with response to treatment [35]. The third major pain theory of the 20th century has been described as a “pattern theory”. The original proponents [51, 68] of this theory argued that pain is generated by intense stimulation of nonspecific nerve endings (or receptors). This theory argued against the specificity notions in favour of spatial and temporal patterns of nerve impulses. This theory was supported into the 1980s. Crue [17], for example, argued that pain is a central percept and not a peripheral primary sensory modality. However, as Bonica and Loeser [12], and others, have pointed out, the theory ignored the physiological evidence that there is a high degree of receptor fibre specialisation. In an attempt to incorporate the growing evidence that psychological factors could influence pain

experience some proponents [33] of the specificity model of pain divided pain into two elements: the perception of pain and the reaction to pain. According to this construction, the perception of pain was seen as primarily a neurophysiological process that was composed of relatively simple neural receptive and conductive mechanisms. In contrast, the reaction to pain was thought to be a more complex physio-psychological process involving cognitive functions, such as past experience and culture, which could influence what they called a pain reaction threshold. However, as Bonica and Loeser [12] pointed out, this model, sometimes called the fourth theory of pain, assumes a one-toone relationship between the intensity of a stimulus and pain perception. In addition, while the idea of a reaction to the perception of pain, perhaps operating like an alarm system, does have face validity, recent studies have indicated that cognitive functions can also influence the perception of noxious stimuli as painful. That does not negate the idea of pain acting as a warning signal, but it does suggest the process is more complex than a simple stimulus-response arrangement. This evidence is examined below.

Modern Perspectives Since the 1960s, there has been a considerable expansion of perspectives on pain. These have been marked by multidimensional constructs that have included neurophysiological, emotional, behavioural, cognitive (meaning) and social/ cultural accounts of pain, either separately or in various combinations. Kleinman [38], for example, described a number of social/cultural perspectives of pain and argued that a reductionist, mechanistic perspective of pain cannot adequately represent the range of experiences, especially in relation to the suffering and impact on lives, reported by many people in pain. Melzack and Wall’s [44] Gate Control Theory of pain might be said to represent an example of an attempt to combine neurophysiological mechanisms with psychological processes, especially cognitions and emotions. In this model, pain was not an inevitable consequence of peripheral stimulation of nociceptors or summated stimulation, but rather an end-product of a number of interacting processes in which the central nervous system, including higher cortical processes like attention and meaning, played an active role in determining the nature and degree of

Psychological Concepts of Pain

pain experienced following noxious stimulation at the periphery. A key feature of the gate theory was that it provided a means of explaining pain that was not dependent upon the nature of the noxious stimulus — a problem that had limited the utility of the specificity/sensory theories. However, the possible impact of environmental influences on the higher cortical functions (such as meaning/ significance; learning; attention), and this might occur, were not directly considered in the early versions of the gate theory. The clinical implications of models of pain like the Gate Control Theory, as well as the social/ cultural perspectives, may be seen in Waddell’s [62] comment that clinicians dealing with back pain should be “treating patients rather than spines, we must approach low-back disability as an illness rather than low-back pain as a purely physical disease”. As a result of these arguments and the evidence on which they were based, a degree of agreement has been reached by the taxonomy committee of the International Association for the Study of Pain [45] which described pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”. The following notes were added by the committee chaired by Merskey [45]: Pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life. It is unquestionably a sensation in a part of the body but it is also always unpleasant and therefore also an emotional experience. Many people report pain in the absence of tissue damage or any likely pathophysiological cause, usually this happens for psychological reasons. There is no way to distinguish their experience from that due to tissue damage, if we take the subjective report. If they regard their experience as pain and if they report it in the same ways as pain caused by tissue damage, it should be accepted as pain. This definition avoids tying pain to the stimulus. Activity induced in the nociceptor and nociceptive pathways by a noxious stimulus is not pain, which is always a psychological

13

state, even though we may well appreciate that pain most often has a proximate physical cause. Some key points to note about this definition include: 1. Pain is considered to be an experience, fundamentally a psychological phenomenon, not an objectively verifiable condition. 2. In addition, the experience of pain involves a mix of sensations and affective qualities. In particular, it is characterised as unpleasant, though the degree of this is likely to vary greatly. 3. Finally, there is acknowledgement that the relationship between pain experience and injury or tissue changes is variable. Thus, we cannot expect to know exactly how “much” pain a person should have with a given injury or tissue damage. While this definition of pain has been generally accepted by pain researchers and clinicians since the early 1980s, it should be noted that its primary focus is the experience of pain and its verbal communication [46]. More recently, some researchers have argued that the definition requires further refinement. For example, Linton [35] suggested an additional aspect should be included in the International Association for the Study of Pain (IASP) definition: that pain is “expressed in behaviour”. Eccleston and Crombez [19] contended that the IASP definition does not stress the affectivemotivational effects of pain on an organism within its natural environment, particularly the role that pain plays in interrupting attention and behaviour and the effect of urging action. As noted earlier, Wall [65] also argued for pain to be seen as a need state, like hunger or thirst, rather than a sensation like seeing or hearing. Wall [67] also argued that the role of attentional processes had been overlooked in the IASP definition. Thus, we should not imagine that the current IASP definition of pain is likely to be the last word on the matter. In contrast to the earlier dualistic notions of pain, where mind and body (pain) were considered as separate domains that underlie the various sensory models of pain, more recent models of pain have emphasised more interactional perspectives. The most widely known, and accepted, of these has come to be known as the biopsychosocial model of pain. Before exploring this it should be noted

14

Michael K. NICHOLAS

that there is no single, accepted model of this name as many versions have been reported and this has led to some confusion in the clinical and research literature [8].

Biopsychosocial Models of Pain Engel’s [21] original biopsychosocial model of illness (which he later elaborated [22]) posited that symptoms should be conceptualised as the result of a dynamic interaction between psychological, social and pathophysiological variables. Engel’s model has since been applied to describing pain phenomena and reviews of empirical support for this model in relation to pain can be found in Turk and Flor [57], Turk and Okifuji [58] and Flor and Hermann [27]. The version of the model applied to pain by Fordyce [29] and Loeser [40], and later elaborated by others [27, 63], incorporates the notions that at the physiological level (i.e. nociception and neuropathy) changes are initiated by trauma or pathology; psychological variables are reflected in the attention and appraisal of internal sensations; and these appraisals and behavioural responses are in turn influenced by social or environmental variables. At the same time, the model also posits that psychological and social variables can influence physiological responses, such as hormone production, activity in the autonomic nervous system and physical deconditioning [57]. For example, behavioural responses, such as avoidance of activity due, say to, fear of pain or expectation of further injury, can result in physical deconditioning and/or greater disability [54, 60]. In this model, nociception is not synonymous with pain. Nociception is only activity in certain neurons, typically generated by noxious stimuli. In the case of pain related to changes in the nervous system (neuropathic pain), there may be no obvious noxious stimuli. This nerve activity does not become pain until it is perceived by the conscious individual — when it is likely to be an immediate focus of attentional processes [13, 19]. The model also separates suffering or the affective aspects of pain from pain perception (typically the more sensory aspects, like burning, sharp,

throbbing). Whether this distinction is justified is the subject of much debate, but it is true that the relationship between pain severity (as measured by intensity rating scales) and distress associated with pain is variable and can be influenced by factors such as the use of coping strategies, cognitions and environmental factors [19, 36]. Evidence for the psychological modulation of pain experience and its impact on the individual is now well established. Key constructs that have been found to be particularly important in this regard are catastrophising (or excessively negative appraisals of pain and other noxious events, such as injury) [53], fear-avoidance beliefs and behaviours [60] and selfefficacy beliefs (the degree of confidence in one’s ability to function or achieve goals despite pain) [49]. Recent research on the role of acceptance of persisting pain has also suggested that this can play an important part in a person’s adaptation to their pain [42]. The ways in which people with persisting pain try to cope with their pain have also been found to make an important contribution to their degree of adjustment. In particular, coping styles (or strategies) deemed to be passive (e.g. excessive resting, relying excessively on medication or other agents and/or other people) have repeatedly been found to be associated with poorer adjustment relative to the use of more active strategies (where the person tries to remain in control as much as possible, as well as keeping active using selfmanagement strategies like activity pacing, goal setting and exercises) [10, 36]. The biopsychosocial perspective of pain can provide a useful framework to make sense of the observed variable relationship between pain severity, physical pathology findings and disability/pain behaviours. It has been found that many people with chronic pain seem to manage quite well, with many continuing to work, to not become distressed or disabled, to use few drugs and to seek medical attention rarely [9, 47]. On the other hand, many people with chronic pain do become distressed and disabled and seek medical care at levels disproportionate to their numbers [9, 11, 30, 47]. It is this latter group that typically appears in pain clinics. By considering these different groups within the framework of the elements of the biopsychosocial model we can see how the impact of different factors might lead to different outcomes even though other aspects of different individuals (e.g. their IASP classification

Psychological Concepts of Pain

or diagnosis) might be the same. Thus, two individuals could both have the diagnosis of failed back surgery syndrome/lumbar spinal or radicular pain after failed spinal surgery, but be quite different in their levels of disability, distress, pain and use of health services. By thinking about these cases in terms of the biopsychosocial model, we might be able to identify possible explanations for these differences and then know what to do about them. A key term commonly associated with this model of pain is pain behaviours. Fordyce [29] defined pain behaviours as what people say, do or do not do which imply to an external observer that tissue damage has occurred. Pain behaviours may include talking or complaining about pain (including rating the severity of pain), taking analgesic medication, lying down during the day, moaning, grimacing, guarding, rubbing or holding a part of the body, ceasing work or domestic chores and visiting a medical practitioner. There is no gold standard or validated definition of pain behaviour, partly because it is likely to vary from one person to the next and one cultural context to the next [56]. The principal test for pain behaviour is that others may infer the behaviour suggests the person displaying it is in pain. Despite difficulties of definition, it is relevant to point out that pain behaviour is the only observable and quantifiable aspect of pain assessment. There are no physiological or strictly objective indices peculiar to pain. People may become distressed, display autonomic changes and withdraw from activities for many reasons other than pain. Thus, the assessment of pain is necessarily dependent upon self-report (by the person in pain). Like all behaviours, pain behaviours are likely to be influenced by both internal (physiological and cognitive) factors and environmental (social and physical) factors. In other words, it should not be assumed that pain behaviours (and pain experience) are totally determined by nociception or pain alone [52]. In this context, Fordyce [29] argued that environmental reinforcement could provide a mechanism for the maintenance of pain behaviours independent of nociception. Although Fordyce was working at a clinical and conceptual level with no scientific evidence for this view, the role of reinforcement in the maintenance of pain behaviours and pain experience has recently been confirmed in a number of experimental studies

15

[28, 34]. The contribution of learning mechanisms in pain has recently been extended further by Flor and colleagues (see below). Some writers, like Waddell and Turk [64], have employed the term “illness behaviour”, developed by Mechanic [43], rather than “pain behaviour”. But they are essentially synonymous, although illness behaviour may be seen as broader in coverage. For Mechanic, illness behaviour is purely descriptive and refers to the ways in which individuals think, feel and act in relation to their health status. Pilowsky [50] makes the point that illness behaviours may be either adaptive or maladaptive. Maladaptive, or pathological behaviours which occur in relation to pain or other illness, Pilowsky calls “abnormal illness behaviour”. This, it must be remembered, is not a diagnosis but refers to a judgement that illness behaviours (including beliefs about illness or pain) are inappropriate in the context of a thorough medical examination ruling out major pathology and attempts at reassurance proving unsuccessful. In this situation, if the patient continues to behave and believe that s/he is ill then these behaviours may be considered or labelled “abnormal”. Like the term “pain behaviour”, “abnormal illness behaviour” is not an explanation of the behaviour — only a description. Causative or treatment implications must be determined by comprehensive assessment of the patient. The role of personality in the experience of pain also has a rich history in the pain literature, but more recently it has been explored mainly within the framework of biopsychosocial perspectives [32]. While some early writers [20] wrote of concepts like a “pain-prone personality”, these views have not been supported in the research literature. More recent approaches have focused on studying interactions between personality traits, cognitive processes, coping skill repertoires and environmental variables in relation to adjustment to chronic pain. For example, there is some evidence that people with personality traits like neuroticism (a tendency to “experience negative, distressing emotions and to possess associated behavioural and cognitive traits” [15]) are more likely to use ineffective coping strategies and to have more adjustment difficulties to persisting pain, compared to those who do not have such traits. Thus, certain personality traits might act as vulnerability factors for difficulties

16

Michael K. NICHOLAS

in adjusting to pain rather than causal factors. Nevertheless, caution is encouraged in this area lest patients be unfairly stigmatised by being branded with pejorative personality labels that could even act as self-fulfilling prophesies by under-treating them or giving inappropriate treatment. It needs to be recognised that methodological shortcomings (e.g. lack of prospective studies) evident in the few studies available preclude the drawing of firm conclusions on the role of personality in this area. Most authorities advise that the interactional perspective outlined here is likely to be the most useful in research into the role of personality and pain [32].

Pain as a Response Rather than a Sensation? Recently, some researchers [6, 27] have argued that pain may be conceptualised as a response, as opposed to a purely sensory phenomenon. This is clearly a major shift from the concepts of pain as a sensation that have dominated much of the pain literature (and clinical practice) for many years. Flor and Hermann [27] described pain as having physiological, behavioural (motor) and subjective (verbal) components, which “may or may not have an underlying pathological basis in the sense of structural change, but will always have physiological antecedents and consequences”. Central to this model of pain is the influence of learning. Based on evidence from a number of laboratory studies, Flor and Hermann argued that learning occurs at the physiological level and that physiological mechanisms could be modified by behavioural and subjective (or cognitive) changes. In this sense, they asserted that the interactions between these different domains were ongoing and not unidirectional. They also considered that this “psychobiological model”, as they called it, was consistent with the IASP definition of pain referred to earlier. But they did suggest that the psychobiological model places more emphasis on the integral role of cognitive and learning factors in the experience of pain as a dynamic process.

Clinical Implications The clinical implications of the biopsychosocial model of pain is that to adequately assess a patient’s pain complaint the clinician(s) must address not only the possible physiological basis of the patient’s symptoms, but also the range of possible psychological and social/environmental variables that have been found to influence pain, distress and disability. These variables, in turn, may then be targeted by appropriate interventions. A medical pain specialist may be most interested in the neuropathic pain generator that is the basis of the patient’s pain. S/he may also be most expert in testing whether a nerve block will reduce or eliminate activity in the fibres and, as a consequence, possibly reduce or eliminate the patient’s pain. However, if other factors (whether cognitive or environmental) are also influencing the patient’s report (and experience) of pain, the purely physical approach of this pain specialist could well fail. Similarly, a psychologist or psychiatrist may be most interested in the cognitive, affective and environmental aspects of a pain problem, but ignorance of what might be happening at the nociceptive or neuropathic levels could well limit their formulation of the case as well as the effectiveness any subsequent treatments or interventions they may offer. At present, it can be argued that attempts to integrate information on the various levels of the biopsychosocial model of pain for any given patient could be described as not much better than a “rule of thumb”. There is no validated way of weighting the contributions of each level on an a priori basis, even assuming that we have adequate measures for each level. Nevertheless, the biopsychosocial conceptualisation of pain does provide a guide as to what might be useful to investigate when assessing an individual and formulating hypotheses to account for the features of the case — hypotheses which can then be tested by targeted interventions patient [64]. Some writers have framed these ideas into ways of answering the question of what works for whom in the field of pain [55, 61].

Psychological Concepts of Pain

17

References 1. 2. 3. 4. 5. 6.

7. 8. 9. 10. 11. 12. 13.

14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27.

28. 29. 30. 31. 32. 33. 34.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 3rd edn. Washington; 1980. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington; 1994. Apkarian AV, Bushnell MC, Treede R-D, et al. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005;9:463–44. Bair MJ, Robinson RL, Katon W, et al. Depression and pain comorbidity: A literature review. Arch Int Med 2003;163:2433–45. Benini A, DeLeo JA. Rene´ Descartes’ Physiology of Pain. Spine 1999;24(20):2115–9. Birbaumer N, Flor H, Lutzenberger W, et al. The corticalization of chronic pain. In Burkhart Bromm, Desmeldt JE, eds. Pain and the Brain: From Nociception to Cognition. Advances in Pain Research and Therapy Vol 22. New York: Raven Press, 1995:331–43. Blumer D, Heilbronn M. Chronic pain as a variant of depressive disease. J Nerv Ment Dis 1982;170:381–406. Blyth FM, Macfarlane G, Nicholas MK. The contribution of psychosocial factors to the development of chronic pain: the key to better outcomes for patients? Pain 2007;129(1-2):8-11. Blyth FM, March LM, Brnabic AJM, et al. Chronic pain in Australia: A prevalence study. Pain 2001;89(2,3):127–34. Blyth FM, March LM, Nicholas MK, et al. Self-management of chronic pain: A population-based study. Pain 2005;113(3):285–92. Blyth FM, March LM, Nicholas MK, et al. Chronic pain, work performance and litigation. Pain 2003;103:41–7. Bonica JJ, Loeser JD. History of pain concepts and therapies. In JJ Bonica, JD Loeser, CR Chapman and WE Fordyce, eds. The Management of Pain, 2nd edn. Volume 1. Philadelphia: Lea and Febiger, 1990:2–17. Chapman CR, Okifuji A. Pain mechanisms and conscious experience. In Dworkin RH, Breitbart WS, eds. Psychosocial Aspects of Pain: A Handbook for Health Care Providers. Progress in Pain Research and Management, Vol 27. Seattle: IASP Press, 2004:3–27. Cherkin DC, Deyo RA, Street JH, et al. Predicting poor outcomes for back pain seen in primary care using patients’ own criteria. Spine 1996;21:2900–7. Costa PT, McCrae RR. Neuroticism, somatic complaint and disease: Is the bark worse than the bite? J Pers 1987;55:299– 316. Cottingham J, Stoothoff R, Murdoch D. The Philosophical Writings of Descartes: Volume 1. New York: Cambridge University Press, 1985. Crue BL. Chronic Pain. New York: SP Medical and Scientific Books 1979: 1952. Eccleston C. Role of psychology in pain management. Br J Anaesth 2001;87:144–52. Eccleston C, Crombez G. Pain demands attention: A cognitive-affective model of the interruptive function of pain. Psychol Bull 1999;125:356–66. Engel GL. Psychogenic pain and the pain-prone patient. Am J Med 1959;26:899–918. Engel GL. The need for a new medical model: A challenge for biomedicine. Science 1977;196:129–36. Engel GL. The clinical application of the biopsychosocial model. Am J Psychiat 1980;37:535. Engel CC, Von Korff M, Katon WJ. Back pain in primary care: Predictors of high health costs. Pain 1996;65:197– 204. Feuerstein M. Definitions of pain. In Tollison CD, ed. Handbook of Chronic Pain Management. Baltimore: Williams & Wilkins, 1989:2–5. Fishbain DA. DSM-IV: Implications and issues for the pain clinician. Am Pain Soc Bull 1995;4:6–18. Fishbain DA, Cutler R, Rosomoff HL, et al. Chronic pain-associated depression: Antecedent or consequence of chronic pain? A review. Clin J Pain 1997;13(2):116–37. Flor H, Hermann C. Biopsychosocial models of pain. In Dworkin RH, Breitbart W, eds. Psychosocial Aspects of Pain: A Handbook for Health Care Providers. Progress in Pain Research and Management, Vol. 27. Seattle: IASP Press, 2004:47– 75. Flor H, Knost B, Birbaumer N. The role of operant conditioning in chronic pain: An experimental investigation. Pain 2002;95:111–8. Fordyce WE. Behavioral Methods for Chronic Pain and Illness, St Louis: CV Mosby, 1976. Frymoyer JW. Back pain and sciatica. N Eng J Med 1988;318:291–300. Gamsa A. The role of psychological factors in chronic pain. Part I. A half century of study. Pain 1994;57:5–15. Gatchel RJ. Comorbidity of chronic pain and mental health disorders: The biopsychosocial perspective. Am Psychol 2004;59:797–805. Hardy JD, Wolff HG, Goodell H. Pain Sensations and Reactions. Baltimore: Williams & Wilkins, 1952. Jolliffe CD, Nicholas MK. Verbally reinforcing pain reports: An experimental test of the operant model of chronic pain. Pain 2004;107:167–75.

18

Michael K. NICHOLAS

35. Karp JF, Scott J, Houck P, et al. Pain predicts longer time to remission during treatment of recurrent depression. J Clin Psychiat 2005;66(5):591–7. 36. Keefe FJ, Rumble ME, Scipio CD, et al. Psychological aspects of persistent pain: Current state of the science. J Pain 2004;5(4):195–211. 37. Kerns RD, Haythornthwaite JA. Depression among chronic pain patients: Cognitive-behavioral analysis and effect on rehabilitation outcome. J Cons Clin Psychol 1988;56:870–6. 38. Kleinman A, Brodwin PE, Good BJ, et al. Pain as human experience: An introduction. In DelVecchio Good M, Brodwin PE, Good BJ, Kleinman A, eds. Pain as Human Experience: An Anthropological Perspective. Berkeley: University of California Press, 1992: 1–14. 39. Linton SJ. Understanding Pain for Better Clinical Practice, 16. Pain Research and Clinical Management Series. Amsterdam: Elsevier, 2005. 40. Loeser JD. Concepts of pain. In Stanton-Hicks M, Boas R, eds. Chronic Low-back Pain. New York: Raven Press, 1982:145–8. 41. Loeser JD, Cousins MJ. Contemporary pain management. Med J Aust 1990;153: 208–16. 42. McCracken LM, Eccleston C. A prospective study of acceptance of pain and patient functioning with chronic pain. Pain 2005;118:164–9. 43. Mechanic D. The concept of illness behaviour. J Chron Dis 1962;156:189–94. 44. Melzack R, Wall PD. Pain mechanisms: A new theory. Science 1965;150:971–9. 45. Merskey H. Pain terms: A list with definitions and notes on usage. Recommended by the IASP Subcommittee on Taxonomy. Pain 1979;6:249–52. 46. Merskey H. Logic, truth and language concepts of pain. Qual Life Res 1984;3: S69–S76. 47. Miedema HS, Chorus AMJ, Wevers CWJ, et al. Chronicity of back problems during working life. Spine 1998;23:2021– 9. 48. Mountcastle VB. Medical Physiology. St. Louis: CV Mosby, 1980. 49. Nicholas MK. The Pain Self-Efficacy Questionnaire: Taking pain into account. Eur J Pain 2007;11:153–63. 50. Pilowsky I. Pain and illness behaviour: assessment and management. In Wall PD, Melzack R, eds. Textbook of Pain, 2nd edn. New York: Churchill Livingstone, 1989:980–8. 51. Sinclair DC. Cutaneous sensation in the doctrine of specific nerve energy. Brain 1955;78:584–614. 52. Stein C. What’s wrong with opioids in chronic pain? Curr Opin Anesthesiol 2000;13:557–9. 53. Sullivan MJ, Lynch ME, Clark AJ. Dimensions of catastrophic thinking associated with pain experience and disability in patients with neuropathic pain conditions. Pain 2005;113:310–5. 54. Troup JDG, Videman T. Inactivity and the aetiopathogenesis of musculoskeletal disorders. Clin Biomech 1989;4:173– 8. 55. Turk DC. Customizing treatment for chronic pain patients: Who, what, and why. Clin J Pain 1990;6:255–70. 56. Turk DC, Flor H. Pain behaviours: The utility and limitations of the pain behaviour construct. Pain 1987;31:277–96. 57. Turk DC, Flor H. Chronic Pain: A biobehavioral perspective. In Gatchel RJ, Turk DC, eds. Psychosocial Factors in Pain: Critical Perspectives. New York: Guilford Press, 1999:18–34. 58. Turk DC and Okifuji A. Psychological factors in chronic pain: Evolution and revolution. J Cons Clin Psychol 2002;70(3):678–90. 59. Turk DC, Rudy TE. Assessment of cognitive factors in chronic pain: A worthwhile enterprise? J Cons Clin Psychol 1986;54,760–8. 60. Vlaeyen JWS, Linton SJ. Fear-avoidance and its consequences in chronic musculoskeletal pain: A state of the art. Pain 2000;85:317–32. 61. Vlaeyen JWS, Morley S. Cognitive-behavioral treatments for chronic pain: What works for whom? Clin J Pain 2005;21:1–8. 62. Waddell G. Clinical assessment of lumbar impairment. Clin Orthop 1987;221:110–20. 63. Waddell G, Bircher M, Finlayson D, et al. Symptoms and signs: Physical disease or illness behaviour? Br Med J 1984;289:739–41. 64. Waddell G, Turk DC. Clinical assessment of low back pain. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: Guilford Press, 1992:15–36. 65. Wall PD. On the relation of injury to pain. Pain 1979;6:253–64. 66. Wall PD. Introduction. In Wall PD, Melzack R, eds. Textbook of Pain, 2nd ed. New York: Churchill Livingstone, 1989:1–18. 67. Wall PD. Introduction to the edition after this one. In PD Wall and R Melzack, eds. The Textbook of Pain, 3rd edn. Edinburgh: Churchill Livingston, 1994:1–7. 68. Weddell G. Somesthesis and the chemical senses. Annu Rev Psychol 1955;6:119–36.

3

Joanne W.Y. CHUNG

Principles of Pain Assessment and Evaluation Tools PAIN AND ASSESSMENT Introduction Role of pain behaviour in pain assessment Significance of multidimensionality in pain assessment PAIN ASSESSMENT TOOLS Visual analogue scale Numerical rating scale Verbal rating scale Brief Pain Inventory McGill Pain Questionnaire CRITIQUE ON PAIN ASSESSMENT TOOLS Sensitivity of unidimensional scales Validity and reliability of unidimensional scales Validity and reliability of multidimensional scales RECENT RESEARCH IN PAIN ASSESSMENT Need for cultural relevancy in pain assessment Assessment of acute pain among Chinese using a verbal rating scale: an exemplar Assessment of cancer pain among Chinese cancer patients: an exemplar REFERENCES

Pain and Assessment Introduction This chapter presents a review of the general guidelines for pain assessment and pain assessment tools. A valid and reliable pain assessment tool is required to measure pain and show treatment effects. Therefore, both the advantages and the disadvantages of the various pain assessment tools are deliberated. Validity and reliability of the tools are addressed. Only commonly used tools are discussed and they include the visual analogue scale, numerical rating scale, verbal rating scale, McGill Pain Questionnaire and the Brief Pain Inventory. In addition, the use of the term “tool” or “scale” throughout the chapter in describing the instrument depends on its conventional naming; in some instances “tool” is a broader term used to include a “scale”.

Role of pain behaviour in pain assessment Pain behaviour is important because an individual’s belief in appropriate pain behaviour affects their exhibition of pain. More importantly, clinicians rely on a patient’s exhibition of pain for diagnosis and treatment, as evidenced by the pain assessment tools that are used in practice [17, 57, 59, 77]. Understanding the patient’s belief in appropriate pain behaviour does have clinical implications for medical practice in pain management [1, 13, 18, 19, 64]. In our diverse health care facilities, we have a wide range of clients with different cultural and ethnic backgrounds. Cultural sensitivity is important in pain assessment [21]. A pain experience is an interaction that reflects an intertwining relationship among biopsychosocial, environmental and political elements. Even within the same culture there can be variation; there is a gender difference among Hong Kong Chinese in their pain report criteria, i.e. the

20

Joanne W.Y. CHUNG

extent of their willingness to express pain [68, 69]. Knowledge and skills related to cultural diversity can strengthen our professional development and practice. It is therefore necessary to have an understanding of beliefs about appropriate pain behaviour in order to better prepare clinicians for the delivery of culturally sensitive pain management regimens.

Significance of multidimensionality in pain assessment The most fundamental aspect of pain relief is the assessment of pain. However, the psychometric attributes are difficult to quantify, making the manifestation of pain experience difficult to assess. Pain is defined as “an unpleasant sensory and emotional experience arising from actual or potential tissue damage or described in terms of such damage” [54]. The emphasis of this definition is on both the sensory and emotional experience of an individual in pain. Pain can be emotional, behavioural, sociocultural and spiritual. The exhibition of pain is multidimensional. Therefore, in the assessment of pain, not only a general guideline for a quick review is needed but also a specific tool to help the professionals to have a more accurate assessment of the experience of pain from a multidimensional perspective. There is no agreement on objective physiological indicators associated with painful episodes. Most of the time, assessment relies on the patients’ verbal pain report. The value of a verbal pain report in the diagnostic process is unquestionable. However, the need for detail and comparatively objective assessment strategies is prevalent and of equal importance in pain relief management. Whether the objectification is accurate and usable in clinical application depends very much on the rigour of the history taking and physical assessment. Pain assessment in clinical practice serves two purposes: diagnostic and algorithmic in pain management. For the diagnostic purpose, a careful history and focused physical assessment are essential. For the algorithmic purpose, pain assessment is crucial in determining the treatment modalities and evaluating the effectiveness of the current pain management regimen.

Pain Assessment Tools The selection of appropriate rating scales is considered a factor for satisfactory pain assessment and pain management [10, 82]. Despite the growing interest in developing multidimensional scales, the use of a unidimensional scale in assessing clinical pain is popular for its simplicity, efficiency and ease of administration [34, 39]. A unidimensional scale can be used on its own as an assessment tool. It can also be used in combination with other scales or tools to provide a multidimensional description of a pain experience. The following provides a description of unidimensional and multidimensional scales. The visual analogue scale (VAS), numerical rating scale (NRS) and categorical rating scale (CRS) [37, 40, 62, 66] are the examples of unidimensional scales while the McGill Pain Questionnaire (MPQ) and Wisconsin Brief Pain Inventory (BPI) are the multidimensional scales. Two organisations, Partner Against Pain and the British Pain Society, provide multilingual pain scales in more than 16 languages. These scales are basically unidimensional scales.

Visual analogue scale The VAS is a 10-cm line with zero representing no pain at one end and 10 representing pain as bad as it could be at the other end (Fig. 3.01). The scales can be presented in different directions. They can be vertical, horizontal or curved [72]. The VAS measures the pain intensity. Patients are asked to report their pain intensity by indicating a point on the line. The distance between zero and the marked point is measured as the pain intensity. The VAS is frequently used in the field of psychology to measure the subjective experiences, e.g. pain, anxiety and nausea [60]. The VAS has been widely used for various types of clinical pain conditions, e.g. acute pain, chronic pain and cancer pain. The VAS is also used in the assessment of dental pain [7]. The VAS has been claimed as the simplest tool in assessing perceived pain intensity [58]. Clinically, it

0 No pain

10 Pain as bad as it could be

Figure 3.01 The visual analogue scale (10 cm)

Principles of Pain Assessment and Evaluation Tools

is easy to administer and there are infinite response options because patients can mark any point on the line [36]. However, the use of VAS requires patients to visualise their pain intensity along a continuum. This requires a considerable amount of abstract thinking. As a result, this limits the use of VAS. For example, children, the elderly, those with cognitive impairment, those with visual impairment and those who are too sick to conceptualise the abstract entity of pain fail in doing the VAS [58]. It had been reported that about 5–7% of patients failed in using the VAS [56, 66]. A similar study conducted among 50 (age range 12–65 years) Chinese patients with postoperative pain to evaluate the reliability of the VAS [2] showed that 14% of the subjects failed to complete the VAS. The reported failure rate is about twice of that reported in Western countries. There was a significant error rate between the vertical and horizontal VAS; in this, the Chinese performed better with the vertical VAS. Considering the level of measurement, the advantage of VAS is the production of a ratio scale judgement that indicates a higher power function [63]. Statistically, this reflects actual perceived pain intensity. Data from the VAS can then be compiled and compared among individuals. However, the statistical manipulation of pain intensity by dividing pain into certain percentages or lengths is deceptive because the scores in the VAS may not be a linear relationship. All assessment tools are subjected to measurement error. Even with its well-established reliability and validity [75], the VAS is no exception. Conventionally, the VAS has to be administered in paper and pencil format. This produces a technical problem with duplicating the VAS because of the alteration in length with the photocopying machine [37]. The possibility of distortion in the length of the VAS contributes to the measurement errors of the instrument. Another drawback of the VAS is that its use involves two stages, i.e. patients marking on the line and subsequent measurement by the assessors [37]. Thus, an extra step in the measurement of scores is required. This results in a potential source of error to the measurement. To overcome this pitfall, there are devices designed on the conceptual basis of a VAS [9]. The visual analogue thermometer (VAT) is one of the examples. The VAT is an instrument with a sliding

21

point along the line. This avoids the second stage measurement otherwise required by the assessor. Despite these drawbacks and controversial arguments, with its simplicity in use and established reliability and validity, the VAS is popular for both clinical and research purposes [29]. It gives good evidence for constructed validity in clinical and research use [46, 58, 66, 75]. The VAS being a validated tool for measuring subjective feelings is therefore frequently used as a gold standard in validating other pain assessment tools, including cancer pain assessment tools.

Numerical rating scale The NRS differs from the VAS in having numbers along a line. The larger the numeral, the greater is the intensity of the pain (Fig. 3.02). Patients are asked to judge along an ordered dimension. For instance, the NRS-101 requires input from a patient who rates his/her pain intensity by indicating a whole number from zero to 100 (Fig. 3.02-a). On the other hand, with the BS-11 (Fig. 3.02-b), 11 boxes are provided; the patient is asked to mark the box that represents his/her pain intensity.

(a) The 101-point numerical rating scale (NRS101) Please indicate on the line below the number between 0 and 100 that best describes your pain. A zero (0) would mean no pain, and a one hundred (100) would mean pain as bad as it could be. Please write only one number. 0 No pain

100 Pain as bad as it could be

(b) The 11-point box scale (BS-11) If a zero (0) means no pain, and a ten means pain as bad as it could be, on this scale of 0 to 10, what is your level of pain? Put an X through that number. 1

2

Figure 3.02

3

4

5

6

7

8

9

10

Samples of numerical rating scale: (a) NRS-101; (b) BS-11.

22

Joanne W.Y. CHUNG

As with the VAS, difficulties in relating pain intensity to the numerals are reported because some abstract thinking is required [5]. This is important from a clinical perspective because patients are likely to be weaker and have a shorter attention span. Therefore, the same restriction on the groups of patients using the NRS applies. In one of the studies reviewing the significance of cancer pain among Chinese patients, the results indicated that about 16–19% of patients failed in using the NRS [15]. Unlike the VAS, the level of measurement of the NRS is ordinal. This means that the scores of the NRS show the changes either by increasing or decreasing but they do not tell the extent of the meaningfulness of the score change. This is because there are infinite points between each successive numeral. However, the NRS has the advantages of easy administration and can be administered in written or verbal format.

ordering of the degree of pain sensation, i.e. the pain intensity but not the emotional component of pain. With cancer pain, patients tend to have some mixed feelings and require more than one category of words to describe them fully [38]. Therefore, their expressions are restricted because the VRS allows the choice of only one response at each time. Second, due to its undimensional property, it offers a restrictive choice of pain words and leads to imprecision in describing pain experience. Third, it has been reported that the VRS is relatively insensitive in evaluating the effect of therapeutic procedure, especially in mild pain [44]. Fourth, unlike the VAS and NRS, it is difficult to compare the results with the same patient over time and with other patients. This is because there is no consistency in the choice of words and

Verbal rating scale The verbal rating scale (VRS), a modification of the CRS, is another unidimensional scale used to measure pain intensity (Fig. 3.03). The VRS measures the cognitive aspect of the perceived pain by the use of pain descriptors. Patients are asked to choose among several given words to quantify their pain rated on an ordinal scale. The advantages of using the VRS are that it is short, easy to administer, easy to score and easily understood by patients. However, there are some inherent disadvantages because of the nature of the scale. First, the VRS only allows a rank

The six-point behavioural rating scale (BRS-6) ( ( ( ( (

(

) No pain ) Pain present, but can easily be ignored ) Pain present, cannot be ignored, but does not interfere with concentration ) Pain present, cannot be ignored, and interferes with concentration ) Pain present, cannot be ignored, interferes with all tasks except taking care of basic needs such as toileting and eating ) Pain present, cannot be ignored, rest or bed rest required

Figure 3.03 The six-point behavioural rating scale.

© The Asian versions (male and female) were developed and copyrighted by C.H. Yeh, PhD, RN and C.H. Wang, Taiwan, 2003.

Figure 3.04 The Asian versions of the Oucher Pain Scale.

Principles of Pain Assessment and Evaluation Tools

the number of verbal descriptions [58]. Fifth, it shares the same mathematical problems as does the NRS in relation to the level of measurement. The distance between each word or descriptor is assumed to be equidistant. Therefore, it does not assess the pain variations between patients and the variations cannot be expressed meaningfully and mathematically. This is especially true for categorical scales, e.g. the Oucher Pain Scale. The Oucher, which was originally developed by Judith E. Beyer, is designed for assessing pain intensity in children aged 3 to 12 years. The Asian version of the Oucher scale was subsequently developed for use in this ethnic group (Fig. 3.04) [78, 81]. It receives similar criticism as any other CRS. The distance between each category is infinite, thus, the statistical manipulation is also argumentative and complex. Sixth, the VRS is criticised as culturally specific. This is because patients have to understand the meanings of the anchored words or descriptors that largely reflect culture of the Western world. Furthermore, illiterates cannot read the words [5].

Brief Pain Inventory The BPI is a refined version of the Wisconsin Brief Pain Questionnaire, which was developed in 1983. It was designed for the assessment of cancer pain. It measures both the location and the effects of pain on the patients’ activities of daily living [49]. There are two versions, the long-form and the shortform. The long version consists of 23 questions while the short version has only nine. The BPI asks about the patients’ pain intensity, location of pain, degree of pain relief, description of pain and the interference of pain with their daily activities [20]. Patients are asked to indicate the extent of the problems using the NRS. For instance, patients are asked to indicate their worst, least and average pain in the past week using the NRS (zero to 10). For the description of pain, patients are provided with 15 pain descriptors. They are asked whether the descriptors apply to their pain or not. In addition, pain history is collected and a body chart is provided for the patients to locate their pain. In summary, the BPI is easy to administer but too brief to be a comprehensive assessment scale.

McGill Pain Questionnaire The MPQ is an example of a multidimensional scale. The MPQ is considered to be the most

23

promising pain assessment tool. The MPQ now has two versions. They are the original longform MPQ and the later-developed short-form MPQ. The MPQ is widely used in various clinical settings. With the introduction of the Gate Control Theory of pain in 1965, Melzack and Casey further postulated three dimensions to elaborate the concepts of pain [51]. The three dimensions are motivational-affective, sensory-discriminative and cognitive-evaluative. In 1971, Melzack and Torgerson then developed the MPQ in an attempt to assess clinical pain [52]. Clinical pain is the pain experienced by the patients during the disease process and not experimentally induced in a laboratory environment. The MPQ comprises a Pain Rating Index (PRI), present pain intensity (PPI) and a choice of pain descriptors to measure the qualities of pain in terms of sensory, affective and evaluative dimensions of pain [51]. The authors believed that the descriptors used could assess the qualities of pain. In the original version of the MPQ, there are 78 pain descriptors. These pain descriptors are grouped into 20 subgroups to reflect the various dimensions of pain. For the scoring system in the MPQ, there are four types of data. The first is a pain rating index that is based on the scale values of all the words chosen in a given class or all classes. It is denoted by PRI (S). The second index obtained is the pain rating index based on the ranked values of the words. It is denoted by PRI (R). The third score is the total number of words chosen from the MPQ, i.e. number of words chosen (NWC). The fourth one is the present pain intensity (PPI), the numerical value obtained from the five-point VRS. The words of the PPI are the words obtained from the evaluative dimensions. The time required to complete an MPQ and its complexity are criticised [9]. The MPQ has been described as lengthy, taking about 15 to 20 minutes to complete. Moreover the descriptors are complex, especially when patients are in pain and ill. Therefore, a short form-MPQ (SF-MPQ) was developed. The SF-MPQ consists of 15 descriptors that describe the sensory and affective dimensions of pain, a PPI and a VAS for the measurement of pain intensity [50]. It takes only 2 to 5 minutes to complete. The SFMPQ was highly correlated with the original MPQ among cancer patients with pain [23].

24

Joanne W.Y. CHUNG

Despite the popularity of the MPQ, there is a limitation in its use among patients. The MPQ requires patients to state their pain experience and some of the patients are too ill to express themselves verbally. Others fail to do so either because of the deterioration in cognitive capacity, a language barrier or no complaint of pain.

Critique on Pain Assessment Tools Sensitivity of unidimensional scales Sensitivity is defined in two different ways, i.e. clinical and statistical. Clinically, sensitivity refers to the number of available response categories for the patients to express their pain. The statistical sensitivity is originated from the psychometric discipline. Statistically, sensitivity of a scale reflects the ability to detect treatment effect. There are controversial arguments in clinical sensitivity of scales. The VAS is claimed to be relatively sensitive because it provides an infinite number of possible responses on a 10-cm line [66]. Conversely, Carlsson argued that the results from the VAS are the subjective estimation of pain intensity and that it is inappropriate for parametric test manipulation [8]. Therefore, the computation in establishing sensitivity is weak. On the other hand, the VRS is criticised as being less sensitive because it has fewer categories [37]. Both the NRS and VRS are criticised for having limited vocabularies for the pain intensity description [66]. Kremer, Atkinson and Ignelzi conducted a study on 56 patients with chronic pain investigating the preference and perceived accuracy of communication for the VAS, NRS and VRS [44]. They concluded that the NRS was the preferred scale because it provided more choices and was more sensitive to changes (r=0.86). However, arguably the sensitivity of a scale does not rely solely on the number of categories available. Conversely, the variability that one offers does increase with the number of categories. This is supported by a study conducted by Jensen, Turner and Romano [40]. One hundred and twenty-four patients with chronic pain were asked to rate their least, most, current and average pain intensity

before and after treatment. The instrument used was the NRS-101. The numbers of the ratings were re-coded to form two-, three-, four-, six-, 11-, and 21-point scales. The correlation coefficients between the re-coded scales and the pain intensity levels were computed. Results showed that the level of sensitivity decreased when the intensity of pain decreased below 11. The best correlation was obtained by the 11- and 21-point scales that were commonly used by the subjects. Furthermore, no scale consistently demonstrates more statistical power than others. Even for a sensitivity scale which produces consistent results, it may not detect a true and an absolute treatment effect. It only provides a relative treatment outcome because pain is subjective. It has been commented that no scale measures the true subjective pain intensity [79].

Validity and reliability of unidimensional scales Reliability is the extent of consistency of a measure upon repeated testing, while validity refers to the extent that a tool measures what it is intended to measure [61]. A valid pain intensity scale should measure pain. A scale, particularly in this context, is for measuring a construct of pain, i.e. intensity. Since scales with greater sensitivity do not necessarily have greater construct validity, the results of statistical power comparisons are not sufficient in themselves for evaluating the validity of an intensity measure [37]. The validity of the scale is evaluated by the correlation between each pain intensity scale and the derived single composite score that best reflects the factors related to pain. This is done by factorial analysis. The single composite score represents the best possible assessment of pain intensity. With the established validity and reliability of the VAS, the VAS is used as a gold standard for the testing of the reliability and validity of other scales. Thus, the reliability and validity of the NRS and VRS are established on the basis of the VAS. Paice and Cohen studied 50 cancer pain patients to test the validity of the VAS, NRS and the Present Pain Intensity (PPI) of the MPQ [58]. The PPI is a type of VRS anchored from “no pain” to “excruciating” on a 6-point scale. Results showed that there is a strong correlation among the VAS, NRS and the

Principles of Pain Assessment and Evaluation Tools

PPI of the MPQ. The basis of argument rests on the established construct validity of the VAS [41]. Hence, the high correlations among the VAS, NRS and PPI supported the validity of the NRS and PPI in the measurement of pain intensity. In other words, the validity issue of the NRS is reflected by the strong positive correlation between the VAS and NRS [45].

Validity and reliability of multidimensional scales The following discussion will focus on the MPQ. The validity and reliability of the MPQ are well documented [20, 27, 43, 74]. The MPQ has been widely used in many clinical situations, e.g. evaluation of the pain responses and the treatment effect, but there is still a lot of disagreement concerning the statistical manipulation. To calculate the changes in pain ratings before and after a pain treatment, it is suggested to change the pain rating into a fraction by having the post-treatment pain rating as the numerator and the sum of the pain ratings for pre- and post-treatment as the denominator [31]. Moreover, Kremer, Atkinson and Ignelzi also commented that the rank order of the pain descriptors in the MPQ affects the precision of the measure [45]. They suggested changing the pain ratings obtained in each dimension into a ratio scale. This is achieved by dividing the sum of rank obtained in each domain by the total rank in that domain. They claimed that this conversion not only provides a ratio measure but also allows comparison among the three dimensions. The method for calculating pain rating has not been settled yet. Criticism has been made that the structure of the MPQ and its analysis methodology are clumsy, i.e. use of factorial analysis to validate the various component of this theory of pain. It was commented that factor analysis of pain descriptors in the MPQ cannot directly evaluate the semantic structure of the questionnaire. Rather, it merely analyses the associative meaning in a specific context [28]. In a meta-analysis of 51 studies involving the use of the MPQ, it was found that ethnicity of the subjects is rarely reported [80]. Therefore, issue of validity is questioned when used across cultures. The MPQ has been translated into different languages and tested in their respective countries for

25

its reliability and validity. Apart from the English version, there are 15 translated versions, namely, Arabic, Chinese, Czech, Danish, Dutch, Finnish, French, German, Hungarian, Italian, Japanese, Norwegian, Polish, Slovak and Spanish [3, 4, 6, 22, 25, 30, 32, 35, 42, 47, 67, 70, 73, 74, 76]. The cross-cultural semantic barrier is a problem that patients and clinicians from countries in nonEnglish speaking areas have to face when using the MPQ [65]. The MPQ was also translated into Chinese for the assessment of headache in Taiwan [35]. Considering the linguistic pain assessment using the MPQ, the results showed that the groups of words chosen by the Chinese patients were different from those of the Westerners. The average number of words chosen (2.43) is less than that of the Westerners (10.5–12). This may be because the words in the Chinese version of the MPQ are translated directly into Chinese using the dictionary. These translated words may not be the words that Chinese would use or there are words that have no Chinese equivalent meaning. Thus, the number 2.43 is questionable and reflects the lack of choice for the Chinese subjects. This is also supported by a study on the use of pain descriptors among Chinese adults in Hong Kong [16].

Recent Research in Pain Assessment Need for cultural relevance in pain assessment The ways in which patients respond to or interpret pain is subject to cultural values [53]. Many studies showed that there is a cultural difference in perception, interpretation and behavioural manifestation of pain [24, 26, 27, 55]. Literature and research from Western countries support that culture is a factor that needs to be considered in pain assessment [71]. However, the current pain assessment tools used in Hong Kong mostly originate from the West. Minimal work has been done on the testing or modification of the pain assessment tools for use with Chinese patients. It is necessary to have assessment tools that are culturally specific so that patients’ experience can best be reflected. The following two examples are

26

Joanne W.Y. CHUNG

of the recent local work done in pain assessment and evaluation.

Assessment of acute pain among Chinese using a verbal rating scale: an exemplar A survey was conducted to explore the pain intensity descriptors used among 986 Chinese [16]. Ten pain intensity descriptors were extracted and were used to construct a verbal rating scale for pain assessment [11]. It consisted of two stages. Stage one was a

cross-sectional descriptive survey to explore the pain intensity descriptors used among adult Chinese in Hong Kong. Stage two was a Q-sorting technique to array the pain intensity descriptors obtained in stage one. Together the results are used to construct a verbal rating scale (VRS) for pain assessment. Nine hundred and eighty-six healthy Chinese adults participated in stage one. The 10 pain intensity descriptors obtained were bearable, crushing the heart and lungs, crucifying pain, excruciating pain, indescribable, quite painful, painful, slight pain, unbearable and very painful. In stage two, 54 baccalaureate-nursing students participated in the Q-sorting procedure. They were asked to rank the pain intensity descriptors according to a set of psychometric criteria. A vertical VRS was constructed with the least pain at the bottom and the most pain on the top. A “no pain” was added to the bottom of the scale. The order of the rank was no pain, slight pain, quite painful, painful, very painful, bearable, indescribable, excruciating pain, unbearable, crushing the heart and lungs and crucifying pain (Fig. 3.05). The psychometric properties of the scale were established by the comparison with the VAS using standardised experimental pain stimulation. The intra-class correlation ranged from 0.78 to 0.90, which indicated good reliability [48]. It is anticipated that a VRS of this kind has its value in the measurement of pain intensity with cultural relevancy.

Assessment of cancer pain among Chinese cancer patients: an exemplar Chung developed the Chinese Cancer Pain Assessment Tool (CCPAT) [13, 14]. The CCPAT is meant to be a specific assessment tool for pain among Chinese cancer patients; assessments involving the general health condition and disease status are not, therefore, included.

Figure 3.05 The Chinese pain intensity scale

The validity and reliability of the CCPAT were tested. Internal consistency was established with a Cronbach’s alpha 0.88 and an inter-rater reliability of 0.96. The Spearman Rho correlations showed that the functional and emotional dimensions of the CCPAT and the present pain intensity of the MPQ were positively correlated. This indicated a satisfactory concurrent validity. The discriminant validity revealed that the CCPAT was able to predict 80.8% of the subjects correctly as cancer patients.

Principles of Pain Assessment and Evaluation Tools

There are three sections in the CCPAT. The first section consists of an instruction guide where a brief description of the CCPAT, administration, steps of assessment, scoring reference and interpretation of the scores are provided. The second section consists of the pain assessment tool. There are six parts in this section. The first part is the functional dimension (13 items), second is psychosocial (5 items), third is pharmacological (8 items), fourth is emotional (8 items), fifth is pain beliefs and meanings (19 items) and sixth is pain intensity (1 item). The third section is a scoring sheet. Upon completion of the assessment, the assessor enters the scores of each part into the designated boxes. The scores are then multiplied by their respective weights. The grand total is obtained by adding up all the weighted scores as instructed in the scoring sheet. The validity of CCPAT was further crossvalidated by using beta-endorphin [12, 33].

27

A true reflection of Chinese cancer patients’ pain experience in their cultural context is crucial in the management of their pain. The developed CCPAT is the first of its kind for the Chinese community in Hong Kong. First, it is envisaged that the study lays the scientific ground for a valid, reliable and cultural-specific tool in the assessment of cancer pain. Second, it is anticipated that the results of the study can provide nurses and doctors with a best possible tool to assess cancer pain. It is significant in the evaluation of patients’ progress and the management of cancer pain. Last but not least, the CCPAT lays the theoretical construct for providing health care professionals with a better understanding of the experience of cancer pain from a multidimensional perspective, and will affect the development of nursing, medical and allied health interventions.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

Al-Obaidi SM, Al-Zoabi B, Al-Shuwaie N, et al. The influence of pain and pain-related fear and disability beliefs on walking velocity in chronic low back pain. Int J Rehab Res 2003;26(2):101–8. Aun C, Lam YM, Collett B. Evaluation of the use of visual analogue scale in Chinese patients. Pain 1986;25:215–21. Bartko D, Kondos M, Jansco S. Slovak version of the McGill-Melzack’s Questionnaire on pain. Cesk Neurol Neurochir 1984;47:113–21. Bende J, Menesi R, Beno U, et al. Hungarian version of McGill Pain Questionnaire. Aneszteziologia es Intenziv Terapia 1993;23:99–103. Bondestam E, Hovgren K, Gaston-Johansson F, et al. Pain assessment by patients and nurses in the early phase of acute myocardial infarction. J Adv Nurs 1987;12:677–82. Boureau F, Luu M, Doubrere JF. Comparative study of the validity of four French McGill Pain Questionnaire (MPQ) versions. Pain 1992;50:59–65. Campbell WI, Lewis S. Visual analogue measurement of pain. Ulster Med J 1990;59(2):149–54. Carlsson AM. Assessment of chronic pain. I. Aspects of the reliability and validity of the visual analogue scale. Pain 1983;16:87–101. Choiniere M, Amsel R. A visual analogue thermometer for measuring pain intensity. J Pain Symptom Manage 1996;11:299–311. Choiniere M, Melzack R, Girard N, et al. Comparisons between patients and nurses assessment of pain and medication efficacy in severe burn injuries. Pain 1990;40:143–52. Chung JWY, Wong CH, Yang JCS, et al. The construction of a pain intensity verbal rating scale in Chinese. Acta Anaesthesiol Sin 1999;37(2):65–71. Chung JWY, Wong TKS, Jessop DS, et al. The relationship between plasma beta-endorphin and the dimensions of the Chinese Cancer Pain Assessment Tool (CCPAT). Pain Clinic 2002;14:33–42. Chung JWY, Wong TKS, Yang YCS. The Lens Model: Assessment of cancer pain in a Chinese context. Cancer Nurs 2000;23(6):454–61. Chung JWY, Wong TKS, Yang YCS. A preliminary report on the Chinese Cancer Pain Assessment Tool (CCPAT): Reliability and validity. Acta Anaesthesiol Sin 2001;39:33–40. Chung JWY, Yang JCS, Wong TKS. Significance of pain among Chinese patients with cancer in Hong Kong. Acta Anaesthesiol Sin 1999;37(1):9–14. Chung WY, Wong CH, Yang JCS, et al. An exploratory study on the use of pain descriptors amongst healthy Chinese adult in Hong Kong. Acta Anaesthesiol Sin 1998;36 (4):S1–11.

28

Joanne W.Y. CHUNG

17. Costardi D, Rozzini L, Costanzi C, et al. The Italian version of the pain assessment in advanced dementia (PAINAD) scale. Arch Gerontol Geriat 2007;44(2):175–80. 18. Crombez G, Vervaet L, Baeyens F, et al. Do pain expectancies cause pain in chronic low back pain patients? A clinical investigation. Behav Res Ther 1996;34:919–25. 19. Crombez G, Vlaeyen JW, Heuts PH, et al. Pain-related fear is more disabling than pain itself: Evidence on the role of pain-related fear in chronic back pain disability. Pain 1999;80:329–39. 20. Daut, RL, Cleeland, CS, Flanery, RC. Development of the Wisconsin Brief Pain Questionnaire to assess pain in cancer and other diseases. Pain 1983;17:197–210. 21. Dindyal S, Dindyal S. How personal factors, including culture and ethnicity, affect the choices and selection of food we make. The Internet Journal of Third World Medicine 2004;1(2). http://www.ispub.com/ostia/index. php?xmlFilePath=journals/ijtwm/vol1n2/food.xml [accessed 24 February 2007] 22. Drewes AM, Helwey-Larsen S, Petersen P, et al. McGill Pain Questionnaire translated into Danish: Experimental and clinical findings. Clin J Pain 1993;9:80–7. 23. Dudgeon D, Raubertas RF, Rosenthal SN. The short-form McGill Pain Questionnaire in chronic cancer pain. J Pain Symptom Manage 1993;8(4):191–5. 24. Faucett J, Gordon N, Levine J. Differences in postoperative pain severity among four ethnic groups. J Pain Symptom Manage 1994;9(6):383–9. 25. Ferracuti S, Romeo G, Leardi MG, et al. New Italian adaptation and standardization of the McGill Pain Questionnaire. Pain 1990;40(Suppl 5):S300. 26. Gaston-Johansson F. Pain assessment: Differences in quality and intensity of the words pain, ache and hurt. Pain 1984;20:69–76. 27. Gaston-Johansson F, Albert M, Fagan E, et al. Similarities in pain descriptions of four different ethnic-culture groups. J Pain Symptom Manage 1990;5(2):94–100. 28. Gracely RH. Evaluation of multidimensional pain scales. Pain 1992;48:297–300. 29. Gross SA. Assessment of cancer pain: A continuous challenge. Support Care Cancer 1994;2:105–10. 30. Harrison A. Arabic pain words. Pain 1988;32:239–50. 31. Hartman LM, Ainsworth KD. Self-regulation of chronic pain. Can J Psychiatry 1980;25:38–43. 32. Hasegawa M, Hattori S, Ishazaki K, et al. The McGill Pain Questionnaire, Japanese version, reconsidered: Confirming the reliability and validity. Pain Research and Management 1996;1:233–7. 33. Ho SS, Chung JWY, Wong TKS. The relationship of plasma beta-endorphins and pain dimensions in primary liver cancer patients using the Chinese Cancer Pain Assessment Tool. Pain Clinic 2006;18 (4):297–313. 34. Holroyd KA, Holm JE, Keefe FJ, et al. A multi-center evaluation of the McGill Pain questionnaire: Results from more than 1,700 chronic pain patients. Pain 1992;48:301–11. 35. Hui YL, Chen ACN. Analysis of the headache in a Chinese patient population. Acta Anaesthesiol Sin 1989;27:13–8. 36. Huskisson EC. Measurement of pain. Lancet 1974;2:1127–31. 37. Jensen MP, Karoly P, Braver S. The measurement of clinical pain intensity: A comparison of six methods. Pain 1986;27:117–26. 38. Jensen MP, Karoly P, Harris P. Assessing the affective component of chronic pain: Development of the Pain Discomfort Scale. J Psychosom Res 1991;35(2/3):149–54. 39. Jensen MP, Karoly P, Huger R. The development and preliminary validation of an instrument to assess patients’ attitudes toward pain. J Psychosom Res 1987;31(3):393–400. 40. Jensen MP, Turner JA, Romano JM. Chronic pain coping measures: Individual versus composite scores. Pain 1992;51:273–80. 41. Joyce CR, Zutshi DW, Hrubes V, et al. Comparison of fixed interval and visual analogue scales for rating chronic pain. Eur J Clin Pharmacol 1975;8:415–20. 42. Ketovuori H, Pontinen PJ. A pain vocabulary in Finnish: The Finnish pain questionnaire. Pain 1981;11:247–253. 43. Kremer E, Atkinson JH. Pain measurement: Construct validity of the affective dimension of the McGill Pain Questionnaire with chronic benign pain patients. Pain 1981;11:93–100. 44. Kremer E, Atkinson JH, Ingelzi RJ. Measurement of pain: Pain preference does not confound pain measurement. Pain 1981a;10:241–8. 45. Kremer E, Atkinson JH, Ingelzi RJ. Pain measurement: The affective dimensional measure of the McGill Pain Questionnaire with a cancer pain population. Pain 1981b;12:153–63. 46. Kuhn S, Cooke K, Collins M, et al. Perceptions of pain relief after surgery. BMJ 1990;300:1687–90. 47. Lazaro C, Bosch F, Torrubia R, et al. The development of a Spanish Questionnaire for assessing pain: Preliminary data concerning reliability and validity. European Journal of Psychological Assessment 1994;10:145–51. 48. Liu JYW, Chung JWY, Wong TKS. The psychometric properties of Chinese Pain Intensity Verbal Rating Scale (CPIVRS). Acta Anaesthesiol Scand 2003;47(8):1013–9. 49. McGuire DB. Comprehensive and multidimensional assessment and measurement of pain. J Pain Symptom Manage 1992;7(5):312–9.

Principles of Pain Assessment and Evaluation Tools

29

50. Melzack R. The short-form McGill Pain Questionnaire. Pain 1987;30:191–7. 51. Melzack R, Casey KL. Sensory, motivational and central control determinants of pain: A conceptual model. In Kenshalo D, ed. The Skin Senses. New York: CC Thomas, 1968:423–43. 52. Melzack R, Katz J. The McGill Pain Questionnaire: Appraisal and current status. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: The Guilford Press, 1992. 53. Melzack R, Wall P. The Challenge of Pain. London, Penguin Books, 1996:15–33, 147–65. 54. Mersky H, Bogduk N, eds. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. Seattle: International Association for the Study of Pain Press, 1994. 55. Moore R, Miller ML, Weinstein P, et al. Cultural perceptions of pain and pain coping among patients and dentists. CommunityDent Oral Epidemiol 1986;14:327–33. 56. Murphy DF, McDonald A, Power C, et al. Measurement of pain: A comparison of the visual analogue with a nonvisual analogue scale. Clin J Pain 1988;3:197–9. 57. Nicholas MK. The pain self-efficacy questionnaire: Taking pain into account. Eur J Pain 2007;11(2):153–63. 58. Paice JA, Cohen FL. Validity of a verbally administered numeric rating scale to measure cancer pain intensity. Cancer Nurs 1997;20(2):88–93. 59. Persson K, Ostman M. The Swedish version of the PACU-Behavioural Pain Rating Scale: A reliable method of assessing postoperative pain? Scand J Caring Sci 2004;18(3):304–9. 60. Polit DF, Hungler BP. Nursing Research: Principles and Methods, 5th edn. Philadelphia: Lippincott, 1995. 61. Portney LG, Watkins MP. Foundations of Clinical Research: Applications to Practice. Norwalk: Appleton & Lange, 1993:53–86, 90–3. 62. Price DD, Bush FM, Long S, et al. A comparison of pain measurement characteristics of mechanical visual analogue and simple numerical rating scales. Pain 1994;2:217–26. 63. Price DD, Harkins SW. Psychophysical approaches to pain measurement and assessment. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: The Guilford Press,1992:111–34. 64. Risdon A, Eccleston C, Crombez G, et al. How can we learn to live with pain? A Q-methodological analysis of the diverse understandings of acceptance of chronic pain. Soc Sci Med 2003;56(2):375–86. 65. Satow A, Nakatani K, Tangiguchi S, et al. Perceptual characteristics of electrocutaneous pain estimated by the 30-word list and visual analog scale. Jpn Psychol Res 1990;32(4):155–64. 66. Scott J, Huskisson EC. Graphic representation of pain. Pain 1976;2:175–84. 67. Sedlak K. A Polish version of the McGill Pain Questionnaire. Pain 1990;(Suppl 5):S300. 68. Soetanto ALF, Chung JWY, Wong TKS. Gender differences in perception: A signal detection theory approach. Acta Anaesthesiol Sin 2004;4:15–22. 69. Soetanto ALF, Chung JWY, Wong TKS. Are there gender differences in pain perception? Journal of Neuroscience Nursing 2006;8(3):172–6. 70. Solcova I, Jacoubek B, Sykora J, et al. Characterization of vertebrogenic pain using the short form of the McGill Pain Questionnaire. Cas Lek Cesk 1990;129:1611–4. 71. Spector RE. Cultural Diversity in Health and Illness, 3rd edn. Norwalk: Appleton and Lange, 1991:47–70. 72. Sriwatanakul K, Kelvie W, Lasagna L, et al. Studies with different types of visual analog scales for measurement of pain. Clin Pharmacol Ther 1983;32:143–8. 73. Stein C, Mend G. The German counterpart to McGill Pain Questionnaire. Pain 1988;32:251–5. 74. Strand LI, Wisnes AR. The development of a Norwegian pain questionnaire. Pain 1991;46:61–6. 75. Vallerand AH. Measurement issues in the comprehensive assessment of cancer pain. Seminars in Oncology Nursing 1997;13(1):16–24. 76. Verkes RJ, Van der Kloot WA, Van der Meij J. The perceived structure of 176 pain descriptive words. Pain 1989;38:219– 29. 77. von Baeyer CL, Spagrud LJ. Systematic review of observational (behavioural) measures of pain for children and adolescents aged 3 to 18 years. Pain 2007;127(1-2):140–50. 78. Wall PD. Melzack R. Textbook of Pain, 3rd edn. Edinburgh: Churchill Livingstone, 1994:307. 79. Wilkie D, Lovejoy N, Dodd M, et al. Cancer pain control behaviors: Description and correlation with pain intensity. Oncol Nurs Forum 1988;15(6):723–31. 80. Wilkie DJ, Savedra MC, Holzemer WL, et al. Use of the McGill Pain Questionnaire to measure pain: A meta-analysis. Nurs Res1990;39(1):36–41. 81. Yeh CH. Development and validation of the Asian version of the Oucher: A pain intensity scale for children. J Pain 2005;6(8):526–34. 82. Zalon ML. Nurses assessment of postoperative patients’ pain. Pain 1993;54:329–34.

4

Paul J. WRIGLEY, Philip J. SIDDALL

The Clinical Evaluation of Pain

INTRODUCTION What is pain? Types of pain Pain is a subjective experience Multidimensional assessment The setting for evaluation Aims of patient evaluation A CLINICAL APPROACH TO ASSESSMENT Pain contributors Pain associated consequences Functional assessment HISTORY TAKING Establishing rapport Details of pain history PHYSICAL EXAMINATION General physical examination Examination of pain behaviours Examination of the painful region Musculoskeletal examination Neurological examination INVESTIGATIONS Clinical neurophysiology Quantitative sensory testing Thermography Brain imaging Response to intervention ASSESSMENT OF SPECIAL POPULATIONS CONCLUSION REFERENCES

Introduction The management of persistent pain and its associated distress remains an enormous problem in global terms. In developed countries, the cost of disability programmes for people with pain are staggeringly high, whether viewed from a medical, occupational or psychosocial perspective [20, 49]. This chapter discusses the principles underlying the assessment of pain, provides a practical approach for assessing people presenting with pain and briefly outlines a number of novel pain investigative approaches.

What is pain? Although this is a basic question and one that has been addressed previously in this book, how we define pain fundamentally influences our approach to the evaluation of pain. It is therefore worth reiterating the definition of pain as put forward by the International Association for the Study of Pain: “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” [39]. Contained within this definition is the concept that pain is not only a sensory experience but is a complex interaction involving emotional and behavioural factors.

Types of pain Pain is often categorised as acute, persistent (chronic) and cancer-related. Persistent pain, the focus of this chapter, has been defined in a number of ways. Some prefer the definition: pain continuing beyond the time of normal healing [2]. However, determining the expected time for healing can be difficult, leading others to use a timeframe of 3 months, beyond which pain is considered persistent. Although common aspects are present across all types of pain, each type varies to some degree in its assessment requirements.

32

Paul J. WRIGLEY, Philip J. SIDDALL

In most acute pain situations, it is appropriate to focus on identifying the source of pain in order to enable treatments to resolve the underlying pathology, or at least relieve the pain. A person with persistent pain, however, may have already undergone multiple investigations and treatments without benefit and may have no identifiable pathology to explain their pain. In this case, it is important that the patient be assisted to move from an “acute, curative approach” to a “longterm, management” approach. In addition to the challenges posed by acute and persistent pain, the person with cancer-related pain may have end of life or existential issues to be addressed.

Pain is a subjective experience …the investigator who would study pain is at the mercy of the patient, upon whose ability and willingness to communicate he is dependent [35] A central factor impeding progress in pain research and treatment is the inherent subjectivity of pain. People commonly express difficulty describing their pain. A common vocabulary for pain does not exist, and as a result individuals with objectively similar conditions often describe vastly different experiences [52]. The subjective nature of the pain experience has been highlighted widely in the pain literature [8, 39, 51]. Despite this, much work has been done attempting to objectify pain assessment. To date, the relationships between pathology, measurement of physical indices, behavioural observation and reports of pain seem to be only weakly correlated [52]. Assessment of the pain experience (hereafter referred to as pain) is therefore largely dependent on patient self-report [31]. Among clinicians, there exists a certain uneasiness when it comes to subjective ratings of pain. The uneasiness rests with perceived discrepancies between verbal reports of pain and what is felt to be “true” pain by the observer. These discrepancies are often due to differences in the way the assessor and the patient view the meaning of the report. It is important to realise that a simple pain intensity measure cannot reflect a person’s pain experience, which is influenced by many factors (see below). Determining whether a pain report is “true” or accurate is less important than determining the

factors contributing to the pain and the effect of the pain on the person.

Multidimensional assessment Given the number of factors affecting the perception of pain, assessment is best performed using a multidimensional model [31, 47]. Each dimension or component does not always co-occur in the same way in all individuals, and is a dynamic process. For humans, the sensory experience of pain contains at least two distinct elements, the generation of a nociceptive or neuropathic sensory trace associated with tissue pathology, and the perception of this trace by the central nervous system (see Chapter 1) [36]. Numerous factors including past experiences, culture, and environmental and genetic factors influence both the perception and expression of pain (see Chapter 2) [11, 40]. Therefore, in evaluating pain, it is important to consider the contribution of biological, psychological and environmental contributors. This interaction of biological, psychological and environmental influences underlies the biopsychosocial model of assessment and treatment of disease, and will be the approach taken throughout this chapter. There is also increasing recognition of the role of spiritual factors in the experience of pain and a comprehensive evaluation of pain will include the interaction of biological (body), psychological (mind) and spiritual (spirit) aspects with the person’s environment (social/physical) as part of the overall assessment. A careful assessment of the patient’s biopsychosocialspiritual system allows the clinician to formulate a rational assessment of the causal links involved in the pain problem. A prioritised problem list and goal-orientated management plan can then be formulated and has been shown to result in better long-term outcomes than unimodal treatment approaches [21]. While the biopsychosocial approach to pain assessment was recommended over 25 years ago [38], it has taken some time to understand the way each element interacts. In recent years, substantial progress has been made, though ongoing refinement continues [19, 21, 24, 54]. A detailed discussion of how these broad elements interact is beyond the scope of this chapter. A pragmatic approach, suitable for use in the busy clinical setting, is however provided in the next section.

The Clinical Evaluation of Pain

The setting for evaluation It is difficult for the sole health practitioner, in a limited period of time, to assess adequately the complicated multidimensional problems presented by a person with persistent pain. This means that, ideally, evaluation is undertaken in the context of a multidisciplinary setting. Such a setting provides the opportunity for a range of health professionals to collaborate in the formulation of an assessment and treatment plan. Typically, such a team comprises experts able to identify pain pathophysiology as well as psychological and environmental factors that may be impacting on the person’s pain perception and behaviour. In a multidisciplinary setting, greater attention to detail can be achieved and members of the team are able to pay particular attention to their area of expertise. The benefits of multidisciplinary treatment are not limited to improvements in pain, mood and function, but have been shown to extend to variables such as return to work and use of the health care system [13, 18, 50]. Although the management of persistent pain ideally occurs in a multidisciplinary setting, this is not always possible. Geographical and financial constraints can mean that these resources are not available. Sole practitioners are often required to assess not only biological factors, but also the elements usually assessed by therapists in other settings. In the absence of a pain assessment team, referral to individual professionals may be an alternative. This of course extends the time required to complete an assessment and poses additional communication difficulties in obtaining management consensus.

Aims of patient evaluation 1. Develop rapport 2. Diagnose treatable medical conditions 3. Assess the contribution of non-biological factors to the pain experience 4. To develop a treatment approach most likely to reduce pain and/or the impact of pain on function. In clinical practice, the primary aim of evaluation is to determine a diagnostic formulation that provides

33

direction for treatment.1 However, an evaluation first allows the development of rapport and trust with the patient. Much of the success of treatment and acceptance of the clinician’s diagnosis and plan for treatment depends on the confidence and relationship established during assessment. This is particularly important where no underlying treatable cause is found to explain the pain, and psychological strategies are suggested to assist in the ongoing management of the problem. An assessment also allows the identification of readily treatable contributors to the pain. It is not uncommon for people with persistent pain to have new symptoms that are not followed up as aggressively or even disregarded because it is assumed that they are part of a persistent benign condition or even of psychological origin. Therefore, the clinician involved in evaluating people with persistent pain must retain a high index of suspicion and avoid dismissing symptoms that may suggest an alternative diagnosis. In addition, a multidimensional assessment can identify important psychological, spiritual and environmental influences on the pain experience. Finally, an assessment needs to identify the impact of the pain on the person. This requires a careful assessment of associated problems and the effect of pain on function (described in more detail below). In addition to biomedical treatments aimed at reducing pain, efforts need to be directed towards reducing the way the pain impacts on the person’s life, i.e. pain management. Once treatment is commenced, ongoing evaluation is important to determine the effectiveness of the treatment. Evaluation may be conducted informally or may be carried out within a rigid protocol such as those used in clinical trials. Obviously, the evaluation requirements of these particular situations are different. This chapter will focus primarily on evaluation in the clinical setting but some of the methods and tools described will be applicable to a more formal evaluation. Traditionally, assessment begins by taking a history and performing a physical examination. These initial steps are followed, where necessary, by the

1. The term diagnostic formulation refers to an outline of potential contributing factors arising from the biological, psychological, environmental and spiritual domains. It is a multidimensional assessment rather than a biomedical assessment, which is commonly implied by the term provisional diagnosis.

34

Paul J. WRIGLEY, Philip J. SIDDALL

performance of further diagnostic procedures that can help to add further information and clarify the diagnosis. Often a provisional diagnostic formulation is proposed following the initial assessment and then modified as further Table 4.01

information is obtained. This approach will be used in this chapter as a framework for examining the specific issues that may need to be considered in the evaluation of the person with persistent pain.

Summary of a pain assessment

(a) History

Examination

Investigation

Pain assessment

TEAM meeting

Review / Collaborative information

(b) 1. Assessment of pain contributors and associated consequences Pain contributors

Pain associated consequences

Biological

Underlying treatable conditions Nociception or neuropathy

e.g. nausea, fatigue

Psychological

Affective disorders Behavioural responses Cognitions

e.g. anxiety, fear avoidance of pain

Social

Family, work, litigation and physical environment

e.g. social isolation

Spiritual

Life view and approach

e.g. loss of faith

2. Functional assessment (Effect of consequences on life roles) Self-maintenance

PADLs and DADLs

Rest

e.g. sleep, relaxation

Leisure

e.g. hobbies or interests

Productivity

e.g. paid and unpaid employment

(a) Performance of a pain history, pain-focused examination and appropriate investigations allows the clinician/assessment team to (b) identifiy pain contributors, determine the presence of pain associated consequences and gauge the effect of pain on function. Assessment findings need to be constantly under review as new information is obtained. PADLs = personal activities of daily living; DADLs = domestic activities of daily living.

The Clinical Evaluation of Pain

A Clinical Approach to Assessment In the clinical setting, it is useful to have a relatively simple overall structure to guide an assessment. For most patients presenting with persistent pain, simple curative treatments are usually not available. Even when a proposed pain “generator” can be removed, this does not necessarily guarantee return to premorbid functioning. With this in mind, assessment needs to allow the development of a reasonable long-term management plan. Assessment may involve the use of standardised questionnaires or rely on the clinician’s judgement. Table 4.02

35

The relative benefit of these two approaches has been long debated [53]. While we will focus in this chapter on clinical judgement, the two approaches need not be considered mutually exclusive. A detailed account of available assessment tools has already been outlined in Chapter 3. We would suggest a pain assessment first attempts to identify pain contributors and associated consequences, and then assesses the effect of pain on function (Table 4.01).

Pain contributors As suggested by others, pain is a dynamic response rather than a simple sensory phenomenon [19]. In

Diagnostic grid of pain contributors

Predisposing

Precipitating

Perpetuating

Biological (Nociception and neuropathy)

Adversive: • genetic • physical developmental factors

Physical stressors: • trauma • inflammation • neuropathy

Poorly controlled: • pathology (e.g. diabetes) • complications from therapies

Psychological

Maladaptive: • attitudes • cognitive abilities • coping style • risk taking behaviour

Psychological stressors: e.g. near death experience

Unhelpful: • cognitions, e.g. catastrophising, fear of pain • behaviours (a) excesses, e.g. medication overuse, reliance on health providers (b) deficits, e.g activityavoidance, poor pacing • coping style, e.g. passive approach • self-efficacy, i.e. low • learning — consequences of and linked associations with behaviour

Social/ environmental

Inadequate: • social support network • institutional support • workplace design (ergonomics)

Adversive external stressors: • social network • occupational • medical system

Inadequate or inappropriate response by: • social support network • occupational network • medical system

Spiritual

• Poor sense of control or responsibility for major life events • Fatalistic perspective • View of God as punishing or cruel

• Failed requests to a god figure to resolve or heal illness • Life crisis which challenges meaning and purpose

• A sense of persecution or punishment • Loss of hope, despair

This table presents a diagnostic grid which can be used to analyse the factors contributing to a person’s persistent pain problem. Examples are given to illustrate each section of the grid. This list is not meant to be exhaustive.

36

Paul J. WRIGLEY, Philip J. SIDDALL

order to develop a management plan it is important to identify the factors contributing to the person’s pain. These contributing factors may predispose, precipitate, or perpetuate a person’s pain. It may also be possible to identify factors that protect a person and assist them in managing persistent pain. In order to organise the large amounts of potential information using this approach, it is suggested a diagnostic grid be employed (Table 4.02). Similar diagnostic grids have been proposed [21].

Biological pain contributors (nociception and neuropathy) From a biomedical point of view, pain can be broadly divided into two main categories based on the structures affected: nociceptive or neuropathic. Nociceptive pain is defined as pain due to activation of primary afferent nociceptive nerve endings by damaging or potentially damaging stimuli. This includes pain arising from pathology in somatic and visceral structures which may resolve (e.g. acute pain following a fractured bone) or be ongoing (e.g. persistent pain associated with degenerative arthritis). In practice, nociceptive pain is almost invariably accompanied by inflammation. Therefore this type of pain is also often referred to as inflammatory pain. Neuropathic pain has been defined as pain initiated or caused by a primary lesion or dysfunction of the nervous system [39]. Nociceptive and neuropathic pains differ in their underlying mechanisms, pain characteristics and response to treatment. Despite emerging evidence suggesting overlap between nociceptive and Table 4.03 Verbal descriptors typical of nociceptive and neuropathic pain Category

Structures affected

Typical descriptors (from [3,4])

Nociceptive

Somatic and visceral

dull tiring heavy

Neuropathic

Peripheral and burning central nervous pressure system squeezing electric shock tingling pricking itching cold

neuropathic mechanisms, these categories remain useful clinically (Table 4.03). While significant debate continues [30], pain occurring in a region of sensory disturbance which is described as burning, pressure, squeezing or electric shock-like is typically considered to be neuropathic in origin [3, 4]. Neuropathic pain can occur in the absence of stimulation (spontaneous pain) or can be evoked. Evoked pain occurs when normally non-painful stimuli such as brushing, light touch and innocuous cold are perceived as painful (allodynia). In contrast, nociceptive pain is typically described as dull, tiring and heavy [4]. Biological factors that may predispose an individual to developing pain may be genetic or related to persistent or past aversive stimuli/trauma (e.g. premature birth with extended neonatal intensive care [16]). Biological pain-perpetuating factors may occur in a number of circumstances including poor disease control, e.g. poor blood sugar control in diabetic peripheral neuropathic pain, or from further damaging stimuli secondary to treatment measures themselves, e.g. scarring following surgery.

Psychological pain contributors The clinician involved in the management of pain needs to be familiar with not only the physical changes that may give rise to the generation of signals in pain pathways but also the emotional, cognitive and environmental influences that may modify the transmission and processing of these signals and thereby impact on the perception and expression of pain. Various psychological models have been proposed to explain chronic pain which influence the approach to evaluation. The Psychoanalytic model views pain to be a result of underlying unconscious conflicts, whereas the Family Systems model proposes that pain is the response to distressed family dynamics. In contrast, the Operant Behavioural model emphasises the importance of consequences in determining how an individual behaves when they are in pain and the Respondent model emphasises the reinforcement of pain by conditioned associations with other stimuli. In addition to these models, there is the Social Modelling theory where learning is said to occur through a process of observation; the Cognitive model, which emphasises the way in which cognitions affect behaviour and mood; and the Cognitive-Behavioural theory, which

The Clinical Evaluation of Pain

acknowledges the importance of reinforcement contingencies but also accepts the influence of cognitive factors. There is little evidence that psychological factors commonly result in pain in the absence of biological precipitating factors. The psychoanalytic model of emotional conflict giving rise to bodily pain has not been readily substantiated [22]. Evidence for psychological factors sustaining pain and its associated distress and disability is more substantial [19, 23, 50]. There is increasing evidence that psychosocial variables are especially important in the transition from acute to chronic disability [37]. Psychological factors include mood, attitudes, cognitions, coping style and risk-taking behaviour. Social factors are discussed in the next section. Psychological contributors are commonly assessed by using both a structured interview (Table 4.04) and a variety of self-report instruments. Self-report instruments may assist in the assessment of affective distress, psychiatric morbidity and functional disability. The goal of a psychological assessment is to identify the psychological factors that affect pain perception, behaviour and function. This information can then be used to develop specific treatment strategies to assist in achieving optimum patient improvement [5].

Social pain contributors Relationships occurring within family and work play an important role in managing the stress associated with ongoing pain. A strong social support network Table 4.04 Aims of a structured interview assessing psychological contributors to pain (based on [42]) Interview aims to determine • Description of current pain problem • Impact of pain on the patient’s life (behavioural deficits and excesses — pain behaviours) • Mood disturbance (and relationship to pain) • Pain cognitions (responses to pain, beliefs about the cause/treatment/outcome) • Pain coping strategies (active/passive) • Patterns of medication use (as required/timebased) • Reinforcement contingencies surrounding pain behaviour (significant others, litigation) • Other stressors present (financial, compensation process, family, losses)

37

and supportive workplace usually facilitates recovery. The presence of dismissive relationships, however, can encourage exaggerated pain behaviours while overly protective relationships may prolong disability by discouraging functional recovery. A common impediment to functional recovery is delayed financial compensation [26]. Lack of social compensation (e.g. requiring an apology for a perceived error) from family, friends or treating practitioners may also slow recovery. In addition, the physical at-work or home environment may predispose an individual to injury (e.g. poor ergonomics) or prevent their return to normal activities (e.g. absence of appropriate access for people requiring wheelchairs to facilitate mobility).

Spiritual contributors Although some link spirituality to religious beliefs, the concept needs to be viewed in a much broader context. Spirituality encompasses a person’s core beliefs (whether framed in religious terms or not) that bring meaning and purpose to their actions, relationships and view of self [9]. A person’s belief structure may therefore profoundly affect behaviours and cognitions in the presence of the challenge of persisting pain [44]. Spiritual beliefs surrounding the meaning and purpose of life can provide a helpful or unhelpful influence on self-management, e.g. belief in evil spirits and the presence of a curse may result in a person relinquishing hope for improvement and remove a sense of control [7]. There is increasing recognition that a person’s spirituality can have a direct contribution to pain and disability and should be part of patient assessment [7, 44]. Some would consider assessment of spirituality part of a broad psychological assessment of beliefs. However, the person conducting the assessment must feel comfortable exploring spiritual issues and be familiar with the evidence describing the contribution of spiritual factors to pain and disability. At times, it may be helpful to have a separate assessment with a person who has appropriate expertise and skills in this area.

Pain associated consequences While the word consequence implies aetiology, its use here is not meant to imply a direct causal link with pain, but to highlight important disturbances associated with the presence of ongoing pain. Once

38

Paul J. WRIGLEY, Philip J. SIDDALL

again, it is helpful to consider consequences in a biopsychosocial-spiritual framework. An enormous range of associated biological consequences are possible. They can be subjective (self-reported), e.g. nausea, palpitations and fatigue, or objective (measured or observed) such as weight loss, oedema or raised blood pressure. Any bodily system may be involved; however, appropriate history taking usually allows targeted questioning. The psychological consequences of longstanding pain (see Chapter 2) are frequently associated with, rather than caused by pain and can include alterations in mood and cognitions. Psychological consequences tend to be more dependent on a combination of factors rather than purely the presence of pain (Table 4.06) [41] including the ability to: • Solve problems

Table 4.05 Psychosocial factors associated with an increased risk of chronic disability (based on [41]) Attitudes and beliefs about pain • Fear that pain means physical damage resulting in avoidance of activity and physical deconditioning • Belief that all pain must be abolished prior to return to work • Catastrophic thoughts about the cause and potential effects of pain • Belief pain is uncontrollable • Expectation of increased pain with increased activity Behaviours • Use of excessive rest/decreased normal activities • Poor compliance with physical activity • Poor pacing skills • Excessive reliance on passive strategies (e.g. massage, medication taking) Mood/emotions • Depressed mood (this may lead to exaggerated negative appraisal of events) • Feelings of uselessness Compensation issues • Lack of financial incentive to return to work • Disputes over eligibility for financial support • Desire for social compensation from family/ friends/treating practitioners

• • • • •

Change unhelpful ways of thinking Improve interaction with other people Develop a graded activity programme Employ behavioural strategies such as pacing and relaxation Develop strategies for medication reduction and improvement in sleep.

Associated social consequences relate to either relational or physical environmental interactions. Important relationships within the family, community or work may change in the presence of ongoing pain. Litigation or other compensation issues may perpetuate a person’s pain associated disability. Other social consequences, such as loss of paid or unpaid employment, may occur resulting in emotional and financial difficulties. In addition, the ability of a person to carry out life roles may be affected. This is discussed in more detail under functional assessment. As mentioned above, a person’s spirituality can directly impact on pain and disability. As might be expected, pain can also have an impact upon a person’s spirituality. On a religious level, persistent pain can make a person question their fundamental beliefs in the nature and even the existence of a supernatural being. On a broader level, persistent pain and disability can influence a person’s view of self, meaning and purpose and give rise to a spiritual crisis that is marked by guilt, sense of failure, abandonment and despair. Most people see the impact of pain in negative terms. However, if a person can draw on positive spiritual beliefs regarding suffering, life purpose and divine support there is an opportunity for growth on a spiritual level. In this circumstance, a person can emerge with a new direction, purpose and meaning that is more robust and outward looking than prior to their pain experience [7].

Functional assessment It is also crucial to assess functional outcomes as part of an overall patient assessment. Indeed, a global need for this approach has been prompted by the recognition that traditional diagnostic data on morbidity and disease do not adequately capture the health outcomes of individuals and populations [48]. The enormous burden imposed on society by health outcomes linked to health conditions has recently been recognised by the World Health Organization as an area of priority [48].

The Clinical Evaluation of Pain

Assessment of function or a person’s ability to carry out a “life role” is a complicated process, and a wide variety of approaches have been developed. A unique vocabulary exists in the literature dealing with functional assessment and rehabilitation. The most recent international guidelines, produced by the World Health Organization, called the International Classification of Functioning, Disability and Health (ICF) were first published in 1999 [57]. While a detailed description is beyond the scope of this text, this model views functioning at three levels namely: the body (bodily function and structure), the whole person (activities) and the whole person in a social context (participation). A formal functional assessment is best performed by health professionals specifically trained in this area. The health professionals most commonly skilled in functional assessment include occupational therapists, physiotherapists, clinical psychologists and medical rehabilitation specialists.

Functional measures While there are a wide variety of outcome measures available, there is general agreement that some measure of physical and emotional function needs to accompany pain measurement when assessing a person with persistent pain. There have been a number of groups working to standardise functional/outcome measures for use in chronic pain clinical practice and research. A consensus statement regarding core outcome measures in clinical trials was recently published (2005) [14]. Measures may be generic or be adapted to specific pain populations, i.e. condition-specific (e.g. spinal cord injury, paediatric pain and pain in the older person). They may involve the administration of questionnaires (self-report) or involve standardised observational measures as undertaken in a Physical Functional Capacity evaluation [1]. There are a range of generic measures that assess global changes in disability/activity including the Sickness Impact Profile (a multidimensional self-report measure) and the Functional Independence Measure (FIM, an observational or self-report measure for physical and cognitive ability). Several condition-specific disability/activity measures are also available including the Roland and Morris Disability Survey and Oswestry Low-Back Pain Disability Questionnaire, commonly used in spinal pain [1]. In spinal cord injury, a new functional measure based on the FIM has been developed, called the Spinal Cord Independence Measure (SCIM) [6].

39

The validity and reliability of the SCIM have been confirmed [27, 28] and the measure is now in its third version, i.e. SCIM III.

Effect on physical function The impact of pain on various aspects of daily living may be assessed using tools that provide information on pain intensity as well as function. These include the Brief Pain Inventory (BPI) and the Multidimensional Pain Inventory (MPI) [33]. A recent consensus statement (IMMPACT) [14] has recommended physical functioning be assessed by either the MPI or BPI interference scales. Assessment of mood Measures commonly used to assess mood in people with chronic pain include the Beck Depression Inventory (BDI) and the Center for Epidemiologic Studies-Depression scale (CES-D) [5]. The measures suggested in the IMMPACT paper are either the BDI or the Profile of Mood States. General measures of participation The Medical Outcomes Study 36-Item ShortForm Health Survey (SF-36) has been used widely to assess levels of participation in a more general social context. It is an eight-scale health survey encompassing physical and mental health. Its use is intended for clinical practice, research, health policy evaluations and general population surveys [1]. To make individual test results useful, the clinician needs to be able to compare the assessment results with normative data obtained from a population sample with similar demographics. Of most benefit is normative data collected from individuals at the same clinic attended by the patient. This enables comparison of the results obtained from an individual with the average patient seen in your clinic or setting.

A brief functional assessment in the clinical setting A simplified clinical approach to functional assessment is also possible. The information required for this can be taken from the history and examination and involves a basic appraisal of a person’s ability to carry out their nominated life roles. Life roles are established through personal need and/or choice and are modified over time based on ability, experience, circumstance and

40

Paul J. WRIGLEY, Philip J. SIDDALL

time. An individual may have many life roles to play, e.g. income provider, father and husband. Most roles can be broken down into four basic areas namely: self-maintenance (activities of daily living), rest (including sleep and relaxation), leisure (activities undertaken for their intrinsic value) and productivity (paid and unpaid employment) (Table 4.06). Problems within any of these areas affect the ability of a person to carry out the roles they play in everyday life [9].

History Taking Establishing rapport It is tempting to jump ahead to taking a history, the first step required in an assessment. However, prior to this, it is important to establish a rapport with the patient. This may seem so basic, as to be unnecessary. However, it cannot be emphasised enough. Trust is a much valued commodity by the patient who has seen many practitioners and Table 4.06 Areas of functional performance Functional performance

Examples

Selfmaintenance (activities of daily living/ ADLs)

• PADLs (personal ADLs), e.g. showering, dressing, grooming, mobilising and transferring • DADLs (domestic ADLs), e.g. cooking, cleaning and shopping + laundry, money management

Rest

The pursuit of “non-activity”, e.g. sleep, rest, relaxation

Leisure

Activities performed for their intrinsic value, e.g. entertainment, creativity and celebration

Productivity

Activities performed for some extrinsic value, e.g. to provide support for self, family or community through the production of goods or provision of services

Problems within any of the above domains can interfere with an individual’s ability to carry out their life roles (based on [9]).

engaged in multiple failed treatments. Patients may harbour a degree of scepticism and bitterness from previous attempts to “cure their pain” and carry with them unhelpful cognitions such as, “They thought the pain was all in my head.” Engaging the patient in effective treatment may be difficult if they do not feel their problem has been adequately assessed and that the clinician is worthy of trust. Conversely, many patients are grateful even in the absence of effective treatment if they feel they have been treated with consideration, thoroughness and care. In developing rapport, it is important to communicate competence in your field, interest in the patient and their problem, and a desire to work to find an answer that will not necessarily cure but help the patient. It is also important to give an indication of what will be involved in the evaluation process as well as the aims.

Details of pain history Taking a patient history is usually the first step towards identifying the main contributors and consequences associated with a person’s pain problem. A history provides information that allows some direction as to whether the pain is primarily somatic, visceral or neuropathic and the contributing psychosocial factors. For example, lumbar spinal pain precipitated by a lifting incident, which is related to movement, eased by rest, with no radiation to the legs, no numbness or paraesthesia and a positive response to simple analgesics, including anti-inflammatory drugs, all suggest a primarily somatic nociceptive pain. In addition, sleep disturbance, loss of appetite and loss of enjoyment of activities suggest an accompanying mood disturbance. A clear history will then provide the basis for further examination and investigations which further refine these preliminary observations. Indeed, a carefully obtained history provides the foundation on which examination and other investigations are built. In addition, the history will provide clues on other aspects of the person’s presentation. The patient’s manner, tone, emphasis of certain facts, expressions and language will all help to convey important aspects of their expectations, understanding of their problem and emotional state. Although there are many variations on taking pain history, the

The Clinical Evaluation of Pain

Table 4.07

41

Outline of pain history (based on [15])

Overview

Pain management

• Reason for referral • Demographics details (including other health providers, medicolegal status)

• Other treatments (present and past, including response) • Medications and substances (present and past, including response) prescription medications complementary and alternative recreational — alcohol, caffeine, tobacco and illicit adverse reactions • Assessment of practitioners’ responses to this patient • Obtain past documentation/collaborative information

Pain description • Onset — mechanism of initiating event. This may provide a clue to what the person thinks is the cause. • Location visceral/somatic radiation (referred/radicular) • Nature/qualities/descriptors nociceptive neuropathic • Temporal characteristics constant episodic • Duration (overall and of episodes) • Intensity (use appropriate intensity scale, present and recent past average) • Aggravating factors • Relieving factors Pain associated consequences and functional ability Problems with self management, rest, leisure and work are determined by assessing the following domains: • Biological (gastrointestinal dysfunction, fatigue, sleep, sexual activity, menstruation, etc.) • Psychological mood (anxiety, depression, anger, despair etc.) cognitions (helpful or unhelpful, concentration, memory etc.) beliefs (regarding pain, illness, self and others) coping strategies (passive, active, fear avoidance etc.) • Social (activities, involvement with others, finance, occupation, leisure, litigation) and physical environment • Spiritual — new life plans, sense of purpose and meaning

basic elements consist of the following: history of the presenting pain problem; effect of the pain on the person (associated consequences and effect on function); previous pain management; and general history (past medical, family, developmental, psychological, social, educational and vocational history (Table 4.07).

General history • • • • • • •

Medical problems past and present Medical problems — family Personal development Psychological history Social context Educational history Vocational history including workers compensation issues

Physical Examination Physical examination assists in: • Developing rapport with the patient • Obtaining further information to support the assessment of pain contributors (structural pathology and psychological behavioural contributors) • Assessing the impact of the pain on physical function. Given the limited time usually available during a clinical assessment, the physical examination is usually relatively focused. A carefully conducted pain history provides significant guidance as to where to direct most attention during examination. Despite this, a general screening examination is also important to check for secondary effects of pain beyond the main reported site. Physical pain generators can be broadly divided into nociceptive or neuropathic. Therefore, the physical examination can be broadly divided into musculoskeletal (or less commonly visceral) and neurological. Other bodily systems (e.g. cardiovascular, respiratory and gastrointestinal)

42

Paul J. WRIGLEY, Philip J. SIDDALL

may also require examination, depending on the individual’s presentation. For example, a poor cardiovascular history in a person with low back pain should alert the clinician to the possibility of an underlying vascular cause. This would then warrant careful examination of the vascular system and potentially further investigation.

The aim of a physical examination is to identify, where possible, the structural problem or the nervous system lesion giving rise to the pain. In addition, any secondary consequences or features of the pain, such as muscle deconditioning, allodynia or hyperalgesia, may need to be a focus of treatment in themselves.

Table 4.08 Assessment of negative and positive symptoms or signs in neuropathic pain (modified from [30]) Sensory symptoms/signs Negative (reduced) • Touch • Pin prick • Cold/heat • Vibration Positive (Spontaneous)

Bedside examination Touch skin with cotton wool Prick skin with pin

A-beta fibres

Specific von Frey, e.g. 5.88 (745mN) Detection/pain threshold cold/warm vibrameter

A-delta fibres

Measure area in cm2 + NRS 11 Measure area in cm2 + NRS 11 Threshold for evocation Measure area in cm2 + NRS 11 Measure area in cm2 + NRS 11

spontaneous activity LT A-beta afferents spontaneous activity C/Adelta afferents spontaneous activity Cnociceptors spontaneous activity Cnociceptors? spontaneous activity joint/muscle nociceptors

Evoked pain to pressure

CS — increased or loss of C fibre input PS

von Frey hair von Frey hair

CS — A-delta fibre input CS — A-delta fibre input

Measure pain duration after stimulus Apply metal roller to skin 20oC Apply metal roller to skin 45oC Topical capsaicin

Measure pain duration after stimulus Threshold and tolerance to cold stimulus Threshold and tolerance to heat stimulus Topical capsaicin

CS

None

Sympathetic block, modulation sympathetic outflow

?

Apply cool (20˚C) and hot (45˚C) tuning fork on malleoli NRS 11 (i.e. grade 0–10)

• Dysaesthesia

NRS 11

• Paroxysms

Number/time + NRS 11

• Superficial burning pain • Deep pain

NRS 11

• Punctate hyperalgesia • Punctate repetitive hyperalgesia (windup-like) • Aftersensation • Cold allodynia • Heat allodynia • Chemical hypersensitivity • Sympathetically maintained

Proposed mechanism

Graded von Frey hair

• Paraesthesia

Positive (Evoked) • Touch evoked allodynia • Static allodynia

Laboratory examination

NRS 11

Brush skin with painter’s brush Gentle mechanical pressure Prick skin with pin Prick skin with pin 2 s for 30 s

A-delta/C fibres A-beta fibres

central sensitization/ disinhibition PS PS

NRS = numerical rating scale, LT = low threshold, CS = central sensitisation, PS = peripheral sensitisation.

The Clinical Evaluation of Pain

When no underlying cause can be identified to explain the pain or an identified underlying disease cannot be cured, conventional examination findings become less useful in guiding management [30]. In these circumstances, a specific pain-focused examination aimed at defining the characteristics of the pain and thereby determining the underlying mechanism(s) of the pain has been suggested (Table 4.08).

General physical examination A general physical examination commences with meeting the patient. Often, a great deal of information can be gleaned even before the patient is seated. Physical observations regarding appearance, posture and gait can be made in addition to informal observations regarding the patient’s mental state including speech, thoughts/ beliefs, orientation, concentration/attention, insight/judgements, affect and illness behaviours.

Examination of pain behaviours People presenting with pain often express distress in a verbal manner, including crying, moaning or complaining. They may also exhibit distress in more physical modes including body postures, facial expressions, medication taking or even visiting health professionals. Systematic approaches for assessing pain behaviours are available and can provide a further measure to assess the pain experience [32]. Observations regarding pain behaviours should not be interpreted in isolation but be part of a more complete multidimensional assessment (biopsychosocial-spiritual). The analysis of pain behaviours can assist in determining the variables influencing behaviour and therefore assist in developing a treatment plan.

Examination of the painful region Inspection Careful attention is paid to the appearance and colour of the skin over the site of pain. Oedema or discolouration may be present, as well as dystrophic changes such as hair loss, increasing sweating, “goosebumps”, pallor or mottling. Palpation Light touch over the region first detects the presence of allodynia. If present, the area of disturbance can

43

be mapped and the distribution (local, regional or dermatomal) determined and correlated with known pathology. The region of hypersensitivity will provide important clues as to whether the pain is due to inflammation, mononeuropathy, polyneuropathy or a central nervous system lesion. If tolerated and musculoskeletal or visceral pathology is suspected, deep pressure using one or more digits can be applied to determine the region of deep tenderness and if possible related to underlying structures. During palpation, the clinician should also observe for any localised or regional responses such as alterations in colour, temperature or sweating, piloerection and muscle spasm. Note is also made of the patient’s generalised reactions such as grimacing, withdrawal, groaning or vocalisation.

Musculoskeletal examination Inspection The patient is inspected anteriorly, posteriorly and from the sides to reveal abnormalities in body shape and symmetry including spinal curvature. Abnormal posture, guarding, stiffness and gait also give clues regarding pathology. Having the patient walk across the examination room allows the detection of gait abnormalities. These may be a result of structural problems such as limb shortening, or may stem from postural changes, weakness or the avoidance of pain. As a screening method for more generalised dysfunction, it is often useful to ask the patient to actively range selected major joints (shoulder, elbow, wrist, hips, knees and ankles) and the spine. An initial “hands off” approach can provide a general assessment of motor function and degree of pain inhibited movement. It also provides another opportunity to observe the patient’s pain behaviours. Palpation Palpation of the region where the pain is perceived will help to detect structures that may be giving rise to pain. Tenderness over specific structures that increases as pressure is applied and giving rise to pain of a similar nature to that reported suggest the generation of pain from these structures. Nonspecific tenderness (generalised or regional) suggests more generalised sensitisation of the nervous system.

44

Paul J. WRIGLEY, Philip J. SIDDALL

Movement Movement of regions involved in the pain will help to determine further the source of the pain (e.g. joint, ligament, etc.) as well as quantify the impact of the pain on function. Joints possibly affected by the pain should be assessed noting active and passive range of motion, pain and other features such as crepitus.

Neurological examination Consensus regarding the best approach to use when assessing neuropathic pain does not exist. Many international clinicians and scientists, however, are attempting to develop a clinically relevant mechanistic-based approach to guide subsequent management decisions. Of central importance to the diagnosis of neuropathic pain is the presence of a sensory transmission disturbance resulting in loss of neural input with corresponding negative sensory symptoms (hypoaesthesia). This reduced sensory input can also initiate broader changes centrally including nerve fibre regeneration and disinhibition resulting in positive sensory symptoms (hyperaesthesia). Positive and negative sensory symptoms can be demonstrated both at the bedside and in the laboratory (Table 4.08) [30].

Sensory Basic evaluation of sensory function includes the assessment of large- and small-fibre function in the region of pain compared with non-painful regions. Testing should at least cover the sensations of touch and pain, using the brush and pin prick tests. Consideration should also be given to the use of other modalities such as proprioception, cold (e.g. applying a metal tuning fork) and heat for a more comprehensive evaluation of fibre and tract function (Table 4.08). Reduction or absence of sensation suggestive of a nerve lesion should be noted. It is also important to note any region of increased sensation (hyperaesthesia), the modality (thermal or mechanical) and the degree of increase (allodynia or hyperalgesia). Positive sensory changes such as allodynia are often used as a diagnostic indicator of neuropathic pain. Such changes however are also present in nociceptive pain conditions and therefore cannot be relied on to identify neuropathic pain. Quantitative sensory testing (described below) may be used in some

situations and enables comparison with normative data as well as changes over time.

Motor The object of motor assessment is to determine the impact of pain upon motor function and to provide further information about a possible neurological lesion. One aspect of motor function is muscle power. Muscles may be tested individually or in groups using standardised dynamometers or more commonly a subjective (five-point) scale. Muscle wasting may be evident through discrepancies in muscle circumference. Other changes in motor function such as increased tone, spasm or tremor should also be noted. Reflexes Deep tendon reflexes and the presence or absence of a Babinski response are assessed to determine the site and level (peripheral or central) of a nerve lesion. Autonomic function This is particularly important in conditions such as complex regional pain syndromes where pain is associated with alterations in autonomic function. The location and nature of changes in temperature, sweating, skin colour, nail and hair growth and oedema should be noted.

Investigations A wide range of investigations may be indicated to complete an assessment of a patient presenting with persistent pain. Unfortunately, while most investigations are able to demonstrate sinister pathology (e.g. fracture, infection, cancer and progressive neurological problems), they do not usually assist in identify the mechanisms underlying persistent pain. For example, in patients with spinal pain, a poor correlation between pain report and the presence of pathology has been shown with anatomical imaging (magnetic resonance imaging of the spine [29, 46]). Therefore, in ordering further investigations, the clinician needs to be clear as to what information they will provide and whether this information is likely to be of benefit in formulating a diagnosis. Continuing to seek a cause for the pain may make the patient and clinician feel that something is being done. However, a nonspecific investigative

The Clinical Evaluation of Pain

approach tends to yield less information over time, adds considerably to medical costs and may delay pain management and functional upgrading. A detailed description of the investigations used in a pain assessment is beyond the scope of this chapter; however, several special investigations, relevant to pain medicine are worthy of further comment. A detailed account of psychophysical measures can be found in Flor (2001) [17].

Clinical neurophysiology Clinical neurophysiology includes electrodiagnostic techniques such as electromyography, nerve conduction studies and somatosensory evoked potentials. These techniques are most likely to be useful for the investigation of neuropathic pain conditions. They may help to provide greater precision in identifying the site of a nerve lesion. Unfortunately they do not assess small-fibre function.

Quantitative sensory testing Quantitative sensory testing involves a detailed, systematic assessment of cutaneous peripheral nerve function (Table 4.08). It is one of the few quantitative ways of assessing small-fibre sensory function [25]. A variety of stimuli are applied to the skin (mechanical, thermal and chemical) which allow more precise information to be obtained regarding the sensory changes associated with pain. The commonly used stimuli include:

Mechanical • von Frey hairs/Semmes-Weinstein Monofilaments: a series of calibrated monofilaments that when applied to the skin produce a calibrated force. These can be used to determine touch (A-beta fibre function) and pain (A-delta/C fibre function) thresholds to a static mechanical stimulus [10]. • A soft brush drawn over the skin can be used to detect the presence of dynamic mechanical allodynia (i.e. pain in response to light touch with movement). Dynamic mechanical allodynia is a measure of central sensitisation, thought to be due to A-beta fibres synapsing with sensitised spinal neurons [30]. • A vibrameter can be used to measure the

vibration threshold function) [10, 43].

(A-alpha/beta

45

fibre

Thermal • Computer-driven thermal testing devices that deliver cold (A-delta fibre) and hot (C fibre) thermal stimuli through a thermode applied to the skin can be used to determine thresholds for sensation and pain [10]. • Thermal rollers, which are kept at a constant temperature (one hot and the other cool), can also be used to detect a decreased (hypoaesthesia) or increased (hyperaesthesia) responsiveness to these stimuli. Chemical • Capsaicin/menthol/histamine can be applied to assess the function of specific A-delta/C fibre subpopulations [30]. Quantitative sensory testing requires specialised equipment and requires additional time to administer. It also relies on the use of normative data, which for some modalities are quite variable. In addition, it relies on patient perception and is therefore more subjective than other neurophysiology investigations, e.g. nerve conduction studies. While it has been used clinically for over three decades [58], time constraints often restrict its use to the research setting.

Thermography Significant controversy surrounds the use of this technique in the assessment of persistent pain[34]. Thermography does not indicate the presence or magnitude of pain but reveals alterations in skin temperature that may be due to changes in vascular or neurological function. Differences in skin temperature can be detected by using an infrared thermometer at different measuring points or with infrared thermal imaging. Measurement of temperature differences may be useful in conditions such as complex regional pain syndrome to detect autonomic dysfunction [45]. It is important to note, however, that the diagnostic sensitivity of static temperature measurement is quite poor in detecting temperature differences between the affected and normal sides. Controlled thermoregulatory studies (where temperature is systematically changed using a thermal suit) are much more sensitive and specific for detecting disturbed autonomic function [55, 56]. This

46

Paul J. WRIGLEY, Philip J. SIDDALL

highlights the importance of assessing dynamic thermal responses. While formal thermal testing may not be possible in the clinic, repeated measurements using, for example, an infrared thermometer in different thermal environments may provide a simpler way of detecting side-toside temperature differences [45].

Brain imaging Conventional neuroimaging techniques based on computer tomography and magnetic resonance imaging are well established in the assessment of gross anatomical structure. More recently, a great deal of interest has been shown in the assessment of function within the central nervous system. Several blood-flow-based neuroimaging methods have become available including positron emission tomography, single positron emission tomography and functional magnetic resonance imaging [17]. In addition, imaging of chemical changes within the central nervous system is possible using magnetic resonance spectroscopy and investigation of changes in electrical activity can be performed using electroencephalography. The use of these newer neuroimaging techniques is still largely confined to research studies. Until further specificity, sensitivity and validity studies are performed relevant to specific disease states, the cost and availability of these investigations will generally preclude use in the clinical setting.

Response to intervention Response to interventions may provide helpful information that further defines pathological processes underlying a pain condition. These include response to drug administration (e.g. phentolamine or intravenous lignocaine) and neural blockade (peripheral and sympathetic nerves). Diagnostic neural blockade may be used to guide pharmacotherapy choices, the use of therapeutic blocks or surgical therapy. The temporary changes afforded by neural blockade may help prior to performing longer-term lesions. The use of a nerve block to identify a particular nerve pathway as a source of a patient’s pain assumes [12]: • A discrete peripheral location generating the pain coupled to a unique neural route • The block will totally and selectively interrupt

•

the sensory function of the targeted nerves Any reduction in pain following the block is due to the blockade of the targeted neural pathway.

These assumptions are limited by the interaction of many variables: • Variation in anatomy • Variation in physiology • The psychology of pain • The variability of local anaesthetic blockade, which is rarely an all-or-none response.

Assessment of Special Populations While the principles described so far are generally applicable to most pain assessments, there are several populations that require more specific assessment tools or approaches. These include children, older people, those with intellectual disabilities and other populations sharing additional factors such as impairment in cognition, physiological differences and communication difficulties. The management of pain in older people, children and adolescents will be discussed in more detail in Chapters 18 and 19. Pain assessment tools specific to these populations have already been discussed in Chapter 3.

Conclusion The clinical evaluation of pain remains an imperfect science. The effectiveness of an evaluation is highly dependent on the health care provider’s preexisting concept of pain, which is itself influenced by personal experience, education and training, and perceived role in the person’s care. While the traditional Western medical model tends to focus on biological pathology and disease management, a purely disease focused approach is inadequate for the management of chronic conditions including persistent pain. It is suggested that a change in focus is required to a biopsychosocial-spiritual model (or wellness model), a model that incorporates predisposing, precipitating and perpetuating factors from the biological, psychological, social/ environmental and spiritual domains and their effect on a person to carry out their life roles. This complex model favours a team approach to patient assessment and care.

The Clinical Evaluation of Pain

47

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33.

Battie MC, May L. Physical and occupational therapy assessment approaches. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: Guilford Press, 2001. Bonica JJ. The Management of Pain. Philadelphia: Lea and Febiger, 1953. Bouhassira D, Attal N, Fermanian J, et al. Development and validation of the Neuropathic Pain Symptom Inventory. Pain 2004;108:248–57. Boureau F, Doubrere JF, Luu M. Study of verbal description in neuropathic pain. Pain 1990;42:145–52. Bradley LA, McKendree-Smith NL. Assessment of psychological status using interviews and self-report instruments. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: Guilford Press, 2001, 292–319. Catz A, Itzkovich M, Agranov E, et al. SCIM — spinal cord independence measure: a new disability scale for patients with spinal cord lesions. Spinal Cord 1997;35:850–6. Chan CLW, Ho RTH, Fu W, et al. Turning curses into blessings: An Eastern approach to psychosocial oncology. J Psychosoc Oncol 2006;24:15–32. Chapman CR, Casey KL, Dubner R, et al. Pain measurement: an overview. Pain 1985; 22:1–31. Chapparo C, Ranka J. Occupational Performance Model (Australia). Retrieved 27 February 2007 from http://www. occupationalperformance.com/oldsite/index.html, 1997. Chong PST, Cros DP. Technology literature review: Quantitative sensory testing. Muscle Nerve 2004;29:734–47. Cleeland CS. Measurement of pain by subjective report. In Chapman CR, Loeser JD, eds. Issues in Pain Measurement. New York: Raven Press, 1989:391–403. Cousins MJ, Walker SM. Neural blockade and pain management. In Max M, ed. Pain 1999 — An Updated Review. Seattle: IASP Press, 1999:281–98. Cutler RB, Fishbain DA, Rosomoff HL, et al. Does nonsurgical pain centre treatment of chronic pain return patients to work? Spine 1994;19:643–52. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain 2005;113:9–19. Faculty of Pain Medicine Australian and New Zealand College of Anaesthetists: Faculty of Pain Medicine trainee support kit. Used with permission, Faculty of Pain Medicine ANZCA, 2006. Fitzgerald M. The development of nociceptive circuits. Nature Reviews Neuroscience 2005;6:507–20. Flor H. Psychophysical assessment of the patient with chronic pain. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: Guilford Press, 2001:76–96. Flor H, Fydrich T, Turk DC. Efficacy of multidisciplinary pain treatment centres: A meta-analytic review. Pain 1992;49:221–30. Flor H, Hermann C, eds. Biopsychosocial Models of Pain. Seattle: IASP Press, 2004. Fordyce WE, ed. Back Pain in the Workplace: Management of Disability in Nonspecific Conditions. Seattle: IASP Press, 1995. Gallagher RM. Rational integration of pharmacologic, behavioral, and rehabilitation strategies in the treatment of chronic pain. Am J Phys Med Rehab 2005;84:S64–S76. Gamsa A. The role of psychological factors in chronic pain. I. A half century of study. Pain 1994;57:5–15. Gamsa A. The role of psychological factors in chronic pain. II. A critical appraisal. Pain 1994;57:17–29. Gatchel RJ. Comorbidity of chronic pain and mental health disorders: The biopsychosocial perspective. Am Psychol 2004;59:795–805. Griffin JW, Hsieh S-T, McArthur JC, et al. Diagnostic testing in neurology. Neurology Clinics 1996;14:119–33. Harris I, Mulford J, Solomon M, et al. Association between compensation status and outcome after surgery. JAMA 2005;293:1644–52. Itzkovich M, Tamir A, Philo O, et al. Reliability of the Catz-Itzkovich spinal cord independence measure assessment by interview and comparison with observation. Am J Phys Med Rehab 2003;82:267–72. Itzkovich M, Tripolski M, Zeilig G, et al. Rash analysis of the Catz-Itzkovich spinal cord independence measure. Spinal Cord 2002;40:396–407. Jensen MC, Brant-Zawadzki MN, Obuchowski N, et al. Magnetic resonance imaging of the lumbar spine in people without back pain. N Eng J Med 1994;331:69–73. Jensen MP, Baron R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003;102:1–8. Jensen MP, Karoly P. Self-report scales and procedures for assessing pain in adults. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: Guilford Press, 2001:15–34. Keefe FJ, Williams DA, Smith SJ. Assessment of pain behaviours. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: Guilford Press, 2001. Kerns RD, Turk DC, Rudy TE. The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain 1985;23:345– 56.

48

Paul J. WRIGLEY, Philip J. SIDDALL

34. LaBorde TC, La L. Reimbursement for unproven therapies: The case of thermography. JAMA 1993;270:2558–9. 35. Lasagna L. Clinical measurement of pain. Ann NY Acad Sci 1960;86:28–37. 36. Light AR, Shults RC, Jones SL. The initial processing of pain and its descending control: Spinal and trigeminal systems. In Gildenberg PL, ed. Pain and Headache. Basel: Karger, 1992. 37. Linton SJ. A review of psychological risk factors in back and neck pain. Spine 2000;25:1148–56. 38. Loeser JD. Concepts of pain. In Stanton-Hicks M, Boas R, eds. Chronic Low-back Pain. New York: Raven Press, 1982:145–8. 39. Merskey H, Bogduk N, eds.Classification of Chronic Pain. Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. Seattle: IASP Press, 1994. 40. Mogil JS, ed. The Genetics of Pain. Seattle: IASP Press, 2004. 41. Nicholas M, Molloy A, Tonkin L, et al. Manage Your Pain: Practical and Positive Ways of Adapting to Chronic Pain. Sydney: ABC books, 2000. 42. Nicholas MK. Structured interview guide for chronic pain patients. Unpublished manuscript, Pain Management Research Institute, Sydney, 1994. 43. Nygaard OP, Mellgren SI. The function of sensory nerve fibres in lumbar radiculopathy: Use of quantitative sensory testing in the exploration of different populations of nerve fibres and dermatomes. Spine 1998;23:348–52. 44. Rippentrop AE, Altmaier EM, Chen JJ, et al. The relationship between religion/spirituality and physical health, mental health, and pain in a chronic pain population. Pain 2005;116:311–21. 45. Rommel O, Habler H-J, Schurmann M. Laboratory tests for complex regional pain syndrome. In Wilson P, StantonHicks M, Harden RN, eds. CRPS: Current Diagnosis and Therapy. Progress in Pain Research and Management. Seattle: IASP Press, 2005: Vol 32. 46. Schellhas KP, Smith MD, Gundry CR, et al. Cervical discogenic pain: Prospective correlation of magnetic resonance imaging and discography in asymptomatic subjects and pain sufferers. Spine 1996;21:300–12. 47. Strong J. Chronic Pain: The Occupational Therapist’s Perspective. Melbourne: Churchill Livingston, 1996. 48. Stucki G. International classification of functioning, disability, and health (ICF). Am J Phys Med Rehab 2005;84:733– 40. 49. Sullivan JML, Standish W, Waite H, et al. Catastrophizing, pain, and disability in patients with soft-tissue injuries. Pain 1998;77:202–8. 50. Turk DC. Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain. Clin J Pain 2002;18:335–65. 51. Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: Guilford Press, 2001. 52. Turk DC, Melzack R. The measurement of pain and the assessment of people experiencing pain. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: Guilford Press, 2001:3–11. 53. Turk DC, Melzack R. Trends and future directions in human pain assessment. In Turk DC, Melzack R, eds. Handbook of Pain Assessment. New York: Guilford Press, 2001:707–15. 54. Turk DC, Okifuji A. Psychological factors in chronic pain: Evolution and revolution. J Consult Clin Psychol 2002;70:678– 90. 55. Wasner G. Skin temperature side differences: a diagnostic tool for CRPS? Pain 2002;98:19–26. 56. Wasner G, Schattschneider J, Heckmann K, et al. Vascular abnormalities in reflex sympathetic dystrophy (CRPS I): mechanisms and diagnositic value. Brain 2001;124:587–99. 57. World Health Organization: International classification of functioning, disability and health. In Geneva, http://www3. who.int/icf/icftemplate.cfmSite, accessed 1 December 2006, 2007. 58. Zaslansky R, Yarnitsky D. Clinical applications of quantitative sensory testing (QST). J Neurol Sci 1998;153:215–38.

5

Mary CARDOSA, Phoon Ping CHEN

Epidemiology in Chronic Pain, Gender and Cultural Aspects

Introduction Epidemiological principles are applied by health care workers as the basis for disease surveillance and investigation. Historically, epidemiology was concerned mainly with investigating epidemics of communicable diseases. Now the application of epidemiological methods has extended to chronic diseases, occupational health and other areas of health care. They are extremely relevant in pain medicine today as it becomes increasingly clear that chronic pain is a major health care concern and public health burden. INTRODUCTION WHAT DOES EPIDEMIOLOGY TELL US ABOUT CHRONIC PAIN? Epidemiological study designs Application of epidemiology in pain medicine Prevalence of chronic pain GENDER AND PAIN ETHNICITY AND CULTURAL ASPECTS OF PAIN Pain reporting Pain relief treatment Reasons for ethnic and racial differences SUMMARY REFERENCES

Epidemiology is defined as the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems [62]. Descriptive epidemiology provides information regarding the health state, personal characteristics of those affected, time and place relating to the occurrence of the event. Analytical epidemiology on the other hand, provides the cause and factors that may influence the event.

What Does Epidemiology Tell Us about Chronic Pain? Epidemiologists employ sound scientific methodology to determine the frequency and pattern of a health-related event in a population and design strategies to control and prevent the event in the community. The distribution of chronic pain is not uniform across different populations and samples, and varies with age, gender, social class, ethnicity, culture and even geography. In studying the epidemiology of chronic pain, many early studies have addressed the question of prevalence, but less attention has been focused on the distribution of chronic pain conditions among different groups in society

50

Mary CARDOSA, Phoon Ping CHEN

Table 5.01 Questions of interest in the epidemiology of low back pain 1. Who are those people who have low back pain — their age, gender, ethnicity, occupation, socioeconomic status, etc.? 2. What is the scale of the problem — how many people have the condition? 3. What is the impact of the low back pain on the people who have it? 4. When did they develop low back pain? 5. How did they acquire the low back pain? 6. Where did they acquire the low back pain? 7. Why do they get low back pain — what is the cause? 8. What factors can influence the condition and its effect?

[29]. In fact, epidemiology research can also allow the study of the distribution of chronic pain and identify the determinants of the condition and its effects across the different groups. Only then we may develop appropriate management strategies to prevent and control this menace. An example of questions asked in an epidemiological study of low back pain is shown in Table 5.01.

Epidemiological study designs The scope of this chapter does not allow for detailed discussion of epidemiological research methods, and only a basic understanding of common methods is presented here. There are generally two types of epidemiological study designs — experimental and observational designs [68]. In an experimental design, the subject is purposely exposed to the possible risk factor and is followed up over time to detect the effect of the exposure. A clinical trial of a treatment that introduces the treatment being studied randomly to subjects who have the health condition being treated is an example of experimental design. In an observational study, samples are drawn from the general population without reference to the health condition being studied or risk-factor status. The exposure and outcome status of each subject are then observed and examined. The most commonly used methods in epidemiology are observational studies. Surveys are commonly used to study chronic pain. These are usually cross-sectional observational studies that investigate the relationship of chronic pain conditions and factors of interest in a specified

population at a particular point of time. A single cross-sectional survey is useful for estimation of prevalence of the chronic pain condition and provides information on its distribution by sociodemographic characteristics. It also allows some inference into the relationship between risk factors such as work-related injury, compensation and chronic pain. However, it is not possible to establish a causal relationship from the study or learn about the natural history of the low back pain from a cross-sectional survey. When subjects in an initial survey are followed over time, the study becomes a longitudinal study. Chronic pain surveys have been conducted on the general population [8, 85], patients registered at general practices [38] and pain clinics [20], populations of a particular pain diagnosis such as back pain [70], neuropathic pain [116] or orofacial pain [77], different occupational groups [51], in older adults [113] and children [90, 96], and on samples in different geographical locations [3, 13]. Many surveys have also focused on different issues including prevalence [30, 85], external factors that influence the severity and impact of the pain condition [10], psychological determinants [14, 15] and impact on individuals and society [9, 64] including economic cost [75]. Two other common epidemiological research designs are the cohort study and case-control study. In the cohort study, the subjects are categorised on the basis of their exposure and then observed over time to see if they develop the chronic pain condition being studied. For example, patients who presented with acute nonspecific low back pain were prescribed bed rest, back exercises or continuation of their normal activities, and then followed up over time to see if they developed chronic low back pain [74]. It is important to note that bias from loss to follow-up, missing data and unreliable measurements in longitudinal study may affect the outcome measurement of the condition being studied. Although conceptually quite similar, a cohort study differs from an experimental design in that the exposure status in the cohort study is observed rather than determined by the study. A cohort study also differs from a repeated crosssectional survey in that the former studies the same group of individuals who participated over a period of time, whereas the latter is usually conducted in different study sample.

Epidemiology in Chronic Pain, Gender and Cultural Aspects

In a case-control study, a group of subjects with the pain condition is compared against a relevant control group, i.e. without the pain condition, to examine their patterns of exposure and to compare their impacts on the pain condition. Case-control studies may be used to estimate the odds ratio for risk factors being studied. One of the main difficulties in this method is the selection of a suitable and most relevant control group. There are a number of potential sources of bias that may affect case-control study and caution is necessary in the interpretation of its results. Some examples of these biases include referral bias, which occurs when the referral patterns cause an over- or under-representation of exposed cases in the study population, ascertainment bias that occurs when there is inaccurate confirmation of either the disease or exposure and admission rate (Berkson) bias that tends to overestimate the exposed cases in a hospital population (in patients with more than one disease, as they are more likely to be hospitalised than patients with one disease) [111]. In epidemiological studies, it is very important to define clearly the particular disease and any factors that are being investigated. The definition of a chronic pain condition may affect the prevalence estimate [125]. As an example, a recent study reviewed two large Canadian population-based surveys that studied the prevalence of pain using two different sets of questions. When the studies were closely examined, they reported that the actual overall prevalence of self-reported pain was 39% for 1-week pain, 66% for 4-week pain and 15% for chronic pain [122]. A standard definition with a set of standard criteria will ensure that all cases are diagnosed in the same way regardless of who makes the diagnosis, or when or where it occurs, and will facilitate the comparison of data at different time and place. Similarly, a standardised methodology in epidemiological research is also important when evaluating similar conditions or risk factors. Otherwise, results will be difficult to repeat and compare [71]. In samples where the definition of pain duration is different, different risk factors and profiles will apply to the different groups. Epidemiological studies must also be conducted on representative samples of the population in order for the findings to have any meaningful and valid generalisation to the respective population groups. A review of epidemiological studies on chronic pain has been reported previously [125]. Detailed

51

discussion of sampling techniques and sample size estimation are described in relevant statistical references.

Application of epidemiology in pain medicine Pain medicine is a relatively new discipline. While pain in some countries may be considered a disease in its own right [104], in most of the developing world, pain is still considered a symptom of some other medical conditions and is treated as such. Epidemiology research has an important role to play in highlighting the extent of the pain problem and in convincing health administrators to consider appropriate health service planning and prioritisation of resources in pain management. Recent epidemiological data have demonstrated that chronic pain is prevalent in our community and represents a major economic burden to our society in terms of high health care utilisation [7, 9], reduced productivity [10, 123], and significant legal costs, social welfare [8] and work-injury compensation claims [11, 20]. In addition, there are also significant psychological and social sufferings, pain-related disability, impairment in quality of life and physical functions in individuals with chronic pain [5, 9, 13, 21, 45, 64, 80, 106]. Epidemiology also has a role in determining the cause of different pain conditions and factors (including risk factors) affecting them. Recent research has indicated that gender and cultural differences may account for some of the differences in pain experience among different groups [61, 66]. Other factors such as psychological “yellow flags” and inadequate coping strategies may contribute to greater risk of disability in chronic pain [52, 60, 69]. This knowledge allows clinicians to devise and implement preventative strategies to reduce the risk of chronic disability and management plans to optimise the ability of chronic pain sufferers to live an active quality life. By determining the pattern of chronic-pain clinical presentations, epidemiological studies also facilitate the identification of different pain diagnostic groups and how they may differ in their relationships with different psychological factors, social circumstances, and other environmental and even aetiological factors, and facilitate the development and design of management strategies.

52

Mary CARDOSA, Phoon Ping CHEN

Epidemiology also promotes best clinical practice, which requires the evaluation of the preventive strategies and assessment of the outcomes of different treatment modalities.

Prevalence of chronic pain The general prevalence of chronic benign pain worldwide ranges from 2–40% with a median prevalence of 15% [125]. The extremes of prevalence rates in this review were obtained in old studies. A recent European survey indicated that the prevalence of pain of longer than 6 months’ duration ranges from 12–30% of the general population [13], with the lowest prevalence rates in Spain (12%), Ireland (13%) and the United Kingdom (13%), and highest prevalence in Norway (30%), Poland (27%) and Italy (26%). Although Norway has the highest prevalence in this survey, an earlier report found that the prevalence was 24% [97]. In Australia, the prevalence of chronic pain was reported to be 17.1% of men and 20% of women [8], while in Canada it was 29% [83]. In Hong Kong, the prevalence of pain of longer than 6 months was reported to be 10.8% [85], although a more recent study found that the prevalence of pain in the preceding 4 weeks before the interview was as high as 45.9% [23]. In South East Asia, the Malaysian’s Third National Health and Morbidity Survey in 2006 found that the prevalence of persistent pain lasting for 3 months or more among adults was 7.1% (Institute for Public Health 2008, Ministry of Health Malaysia). The prevalence in Singapore was similar to that of Malaysia, while the Philippines and India reported rates closer to that of Australia and Europe (personal communication). The prevalence of neuropathic pain has been reported to be 8% in Scotland, compared with a prevalence of 48% for any chronic pain [107, 116]. Unlike previous studies, neuropathic pain in this survey was diagnosed using the Self-complete Leeds Assessment of Neuropathic Symptoms and Signs score (S-LANSS). The authors reported that respondents with neuropathic pain had higher pain intensity, longer duration of pain, poorer health and greater disability, according to Short Form (36) Health Survey (SF-36) and Brief Pain Inventory scores. A similar impact on quality of life was reported previously [79]. The epidemiology of pain in children has not been well documented. The prevalence of chronic pain

in children and adolescents has been reported to be 30.8% (pain >6 months) in a district in Germany [96] and 25% (pain >3 months) in the Netherlands [90]. In the German survey (n=749), the most common pain types were headache (60.5%), abdominal pain (43.3%), limb pain (33.6%) and back pain (30.2%) resulting in sleep problems (53.6%), inability to pursue hobbies (53.3%), eating problems (51.1%) and school absence (48.8%). Unlike pain in the other extreme of age, pain in children has not been given the attention it warrants. Greater focus on research and clinical pain management should be promoted in this group of pain sufferers. More information on chronic pain in children is covered in Chapter 19. Chronic pain affects more than 50% of older persons living in the community setting, and more than 80% of nursing home residents [40, 49]. In another study, 45.8% of older persons admitted to US teaching hospitals reported pain, with19% having severe pain and 12.9% dissatisfied with their analgesia [33]. A study of older Chinese patients attending outpatient clinics in Hong Kong found that 61.5% of patients had experienced pain in the recent 2 weeks, with over half requiring pain relief medications [80]. In developed countries, the percentage of the population over 65 years old will rise from 17.5% to 36.3% by 2050, and the over-80 age group will more than triple [121]. As the world’s population is living longer and getting older, epidemiology of pain in the older persons has become more important for the planning of future health care needs of this group. Chronic pain in older adults is often caused by more than one clinical diagnosis [53]. Common conditions causing pain in the older person include osteoarthritis, postherpetic neuralgia, spinal canal stenosis, cancer, fibromyalgia, poststroke pain and diabetic peripheral neuropathy. In a previous population survey, age older than 60 years was identified as a risk factor for chronic pain [85]. Older adults with chronic pain had more intense pain (median VAS pain score 7.5 compared with 5.0 in younger sufferers) and were more severely affected by their pain. Older patients with pain had poorer sleep quality, lower self-rated health status and a higher proportion of depression when compared with those in the same

Epidemiology in Chronic Pain, Gender and Cultural Aspects

age group without pain [80]. More information on chronic pain in the older person can be found in Chapter 18. The prevalence of common pain conditions such as back pain, headache, orofacial, joint or cancer pain will be described in the respective sections. The epidemiology of risk factors, preventive measures and treatment strategies will also be discussed elsewhere in the relevant sections.

Gender and Pain Population-based epidemiological studies have shown a higher prevalence of chronic pain in women than men [8, 13]. In addition, many studies have shown that a number of chronic pain conditions are more commonly seen in women than men and these include headaches and migraines [99, 87], temporomandibular disorders [17], abdominal pain [57], irritable bowel syndrome [48] and widespread painful conditions like fibromyalgia [16, 129]. It is also frequently reported that women have a higher risk than men for multiple pain conditions [6]. The differences in the experience of pain between the men and women relate to both sex and gender. The term “sex” refers to the biological aspects of identity such as whether the individual has XX or XY chromosomes, whereas “gender” is more related to societal influences and expression of masculinity or femininity [66]. A study on gender differences in pain experiences to experimentally induced thermal pain among a Chinese population have found that women were more sensitive and less stoic in responding to pain than men [109]. In a subsequent study, the author found that women had a lower threshold and tolerance for pressure pain than men [108]. In another study on gender differences in Chinese subjects with osteoarthritis, Tsai reported that Chinese women reported greater pain intensity and interference from osteoarthritis, and had a greater depressive tendency [117]. This study found that depression was the mediator of gender differences and cautioned against the use of gender differences to explain the experience of pain among Chinese elders. These studies indicated that careful interpretation of gender differences is required when reviewing epidemiological studies.

53

While the evidence suggests that women are more likely to experience pain conditions than men, the pattern and differences may be affected by age. Neck and shoulder pain was reported to be more prevalent in Norwegian women, and increased with age [47], while abdominal pain, although more prevalent in Swedish women compared with men, decreased with age [1]. Migraine, on the other hand, has a bell-shaped distribution over the adult age groups, with the largest difference in femalemale prevalence in the middle years [99]. When interpreting epidemiological studies, age- and gender-specific prevalence patterns must be taken into account as they differ among the different pain conditions. This is important as they provide information about the factors that influence the occurrence of the pain condition and thus facilitate strategies to prevent and manage these conditions. While gender differences in pain sensitivity are partly attributable to social conditioning and psychosocial factors, many studies have now indicated that biological mechanisms underlie such differences. Studies on sex differences in the response to analgesics have indicated that pain modulation mechanisms may be different between men and women. Research on transgenic mice has suggested that normal males have a higher level of endogenous analgesic activity, while human studies have found that mu- as well as kappa-receptors activation and responses are different between the genders [128]. Well-controlled studies have increasingly shown that the gender differences in opioid analgesia depend on many interacting variables including gonadal hormonal effects, pharmacokinetics and pharmacodynamics, genetic influences and balance in analgesic/antianalgesic processes [31, 41]. There is evidence that gonadal steroid hormones such as oestradiol and testosterone modulate sensitivity to pain and analgesia [27, 42, 66]. Recently, a study in rats has shown that gender differences in the basal expression and the modulation of the N-methyl-Daspartate receptor activities in dorsal root ganglia neurons are regulated by sex hormones [78]. Advances in molecular biological technology have allowed the cloning, mapping and sequencing of genes, and also the ability to disrupt their function entirely facilitating genetic research in pain [81]. Polymorphisms in genes coding in the neurotransmitter and receptor systems have also been shown to influence the variability of pain responses in individuals [35], and some of these genetic variations

54

Mary CARDOSA, Phoon Ping CHEN

may in fact be associated with the pathogenesis of conditions such as fibromyalgia syndrome where there is a higher preponderance in women [16]. In the study by Tsai [117] above, the depressionmediated gender differences in osteoarthritic pain and disability may in fact have a genetic basis. More recently, X- or Y-linked genes have been indicated to have direct effects in acute nociception, not mediated by gonadal secretions [43]. Craft and colleagues indicated that sex differences in pain and analgesia may be both quantitative and qualitative in nature. They envisioned that sex-specific management of clinical pain may be a reality in the not-so-distant future [27]. While biological differences leading to increased sensitivity to painful stimuli have been postulated as one of the reasons for the observed difference in prevalence of chronic pain between the sexes, the relationship between gender and pain is more complex [65]. Women have been shown to report more severe clinical pain [118] and experimentally induced pain than men [94]. When examined closely within different age groups, women do not report more pain for every pain condition, and different pain problems may show differing patterns. Psychosocial factors such as life-cycle changes, social and occupational role expectations, cognitive and emotional experiences of pain, and different coping approaches and skills play an important role in determining gender differences in pain prevalence [58, 65] and contribute to a higher prevalence in women. These apparent differences may also reflect the way men and women respond to pain, and that there are different social norms for the expression of pain [32]. In one experimental study, female subjects were found to have lower tolerances than male subjects to the pain stimulus [92]. However, interestingly, reports of pain by male subjects were affected by the gender of observer. Significantly less pain was reported in front of a female experimenter than a male experimenter, whereas in female subjects, there was no difference [67]. Women are generally more willing to report pain than men in Western culture [94] and more likely to seek health care [119]. Women with pain conditions were reported to use a broader range of coping strategies than men, and reported more problem solving and positive statements [120]. They also sought more social support than men.

These experiences are more likely associated with psychological, environmental, social and cultural influences than biological reasons.

Ethnicity and Cultural Aspects of Pain Differences in responses to pain have been observed in various racial groups within and between countries. Although the terms “race”, “ethnicity” and “culture” are often used interchangeably, race is thought to be biologically determined, while ethnicity and culture are social constructs [76]. According to the biopsychosocial model of pain, however, it would seem that ethnicity and culture would be just as important as contributors to chronic pain as biological factors (race). Both laboratory and clinical studies have shown evidence that people of different ethnicity and cultures respond differently to pain. Ethnic differences in experimental pain perception have been documented from as early as 1944 when Chapman and Jones reported lower heat pain thresholds and tolerances among African-American subjects compared to non-Hispanic Caucasian subjects [19]. Subsequently, there have been other studies reporting similar findings, and more recent publications have added to the information on ethnic differences, giving an overall picture of reduced tolerance to experimentally induced pain stimuli in African-Americans compared to Caucasians [36, 37, 38, 103].

Pain reporting In a study of postoperative dental pain, Faucett showed that Americans of European descent reported significantly less pain than Americans of African and Latino descent [39]. Similarly, other studies comparing African-Americans and Caucasians have shown that African-Americans reported more pain than Caucasians after spinal surgery [127] as well as among those who experienced treadmill-induced angina [102]. However, there were also studies that showed no ethnic difference in pain reports in other acute situations such as in post-trauma pain [115]. In chronic pain conditions, African-Americans have also been reported to have higher levels of pain compared to non-Hispanic Caucasians with

Epidemiology in Chronic Pain, Gender and Cultural Aspects

several painful conditions, including acquired immune deficiency syndrome (AIDS) [12], arthritis [28] and low back pain [101]. In a study of chronic pain patients attending a pain clinic, while pain severity scores were no different, AfricanAmericans reported higher levels of pain-related unpleasantness, depression and fear, and scored higher on scales related to pain behaviour compared with non-Hispanic white Americans [93]. A recent study of musculoskeletal pain in Malaysia reported that the pain rating was higher in women (23.8%) than in men (17.8%) [124]. Among the multiracial population, Chinese men reported the lowest agestandardised pain rating (9.9%), while Indian women had the highest rating (28.4%). It is noteworthy that the tools for pain assessment may present cultural biases when they are used in individuals of different ethnicity as there may be an inherent difficulty to conceptualise and quantify pain. In a study of Aboriginals and Torres Strait Islanders, it was found that 15.8% of the group was unable to use the numeric rating scale [98], while another study reported that 19% of Chinese cancer patients had difficulty with the same tool [24]. In addition, different ethnic groups and cultures may use different pain descriptors that may be interpreted differently outside the group. In one Chinese study, crucifying pain (10/10) was the most severe descriptor compared with unbearable (7/10) or indescribable pain (6/10) [22]. Another study reported that a vertical visual analogue scoring scale may be more appropriate for the Chinese patients as the Chinese language is traditionally written and read from top to bottom [2].

Pain relief treatment Studies have shown that ethnicity was a significant predictor of the dose of postoperative opioid analgesia prescribed by clinicians [63]. Pharmacogenetic differences between ethnic groups may lead to polymorphism in metabolising ability (enzyme CYP2D6) and result in variation in response to some pain relief medications. Chinese, for example, have a lower prevalence of poor metabolisers and a higher sensitivity to some medications such as codeine [91, 130]. In cases where the analgesia was self-administered by a patient-controlled analgesia technique, earlier studies had found that the eventual dose of opioids consumed was no different between patients of

55

different ethnicities [84, 118]. However, in a more recent report of self-rated pain score and patientcontrolled morphine usage in 1,034 women after elective lower Caesarean section, the authors found that patients of Indian race in Singapore had the highest mean pain score and consumed the highest amounts of morphine [112]; this is similar to findings in another study on chronic pain [124]. There is also evidence that male and female clinicians may respond differently to the demographic characteristics of patients in need of pain management [126]. A recent survey of patients with long bone fractures presenting at an emergency department found that white patients were more likely than black to receive analgesics [114]. The risk of a black patient not receiving analgesic at the emergency department was 66% greater than for white patients. Stereotyping ethnic groups in their responses to pain may lead to under-treatment in the affected groups. In another study of patients after cholecystectomy, it was found that Chinese, Japanese and Filipino patients received less pain medications than Caucasians and Hawaiians [110]. The authors reasoned that the differences may be related to ethnic differences in analgesic requirement or cultural bias. Some cultural styles (East Asians are more stoic) may be more susceptible to undertreatment than others.

Reasons for ethnic and racial differences in pain A variety of biological, social and psychological mechanisms may be responsible for observed racial and ethnic differences in pain reports. Increasingly more studies have examined whether biological (genetic) or sociocultural factors could account for these differences in pain responses, or whether these factors are influenced by the environment (the nature-nurture argument).

Biological factors The mutation of the gene SCN9A that leaves the individual completely insensitive to pain has recently been mapped [26, 44]. It is becoming clearer that other genetic polymorphisms or gene mutations may also make individuals more sensitive or susceptible to pain, especially to the development of chronic persistent pain [82].

56

Mary CARDOSA, Phoon Ping CHEN

Recent research has found that the risk for developing intervertebral disc degeneration and its severity is associated with genetic risk factors and is highly heritable [56, 133]. Two of these genetic variants are encoded by the Trp2 and Trp3 alleles in the COL9A2 and COL9A3 genes. While the Trp3 (but not Trp2) allele has been shown to be more prevalent in Caucasians (Finnish), it is absent in the Southern Chinese population [50]. Contrary to this, in Southern Chinese the Trp2 allele is a significant risk factor for developing severe intervertebral disc degeneration, annular tears and herniations. The contrasting Trp allele frequencies between the Caucasians and the Chinese indicate that the genetic risk factors may vary between different races. It is also possible that cultural and ethnic factors can influence activity in higher nervous centres that modulate pain through the activation of descending neural inhibitory controls [34]. There is some evidence that ethnic differences in pain perception may be influenced by differences in descending neural inhibitory controls [18]. This mechanism may account for the observation in Hindu devotees who are able to tolerate the piercing of their body with sharp objects during the Thaipusam rituals which occur every year in countries like Malaysia. Similarly, cultural norms could account for the fact that in China, even young children are able to accept having acupuncture done to them as a treatment for any ailment, in contrast to the experience in Western medicine settings where injections are avoided as far as possible when treating paediatric patients because of children’s fear of needles. Cultural practices such as meditation may also modulate pain responses. Kakigi showed that there was a marked reduction in functional magnetic resonance imaging activity in the thalamus, insula and cingulated cortex with the same painful stimulus during meditation [55]. In a non-meditative state, the subject reported pain scores of 8/10 compared to 0/10 in response to the same stimulus when he was in deep meditation.

Psychosocial factors Psychological factors including different pain coping styles of different ethnic groups may lead to differences in the report of pain and subsequent disability [34]. African-Americans with rheumatoid arthritis reported significantly greater use of

distraction and passive coping mechanisms like praying and hoping, while Caucasians reported more use of ignoring pain and a greater perceived ability to control pain [54]. Ethnic minorities are also more likely to experience high levels of chronic stress due to social discrimination and racism [34]. This stress produces chronically high levels of sympathetic activation and physiological exhaustion [25], and leads to limited coping resources, which in turn makes it more difficult to deal with persistent pain [34]. Social factors including socioeconomic status and ethnic background can affect access to health care. Under-treatment of pain in minority populations has been previously reported [105, 110]. As unrelieved acute pain increases the risk of developing chronic pain states [59, 89], patients from socially disadvantaged groups may be more at risk of being exposed to unrelieved pain [34]. Furthermore, lack of trust of patients from ethnic minority groups in their physicians [46] may lead to delay in seeking health care, which in turn increases risk of having unrelieved pain. Ethnic factors may influence the appraisal of pain and the subsequent responses. The meaning of pain may be influenced by sociocultural factors, for example, pain as retribution or pain as something to be mastered [4]. This can have a major influence on both emotional and behavioural responses, including the decision whether to seek treatment and from whom to seek treatment. There is now evidence that cultural factors such as health beliefs and expectation may affect common musculoskeletal symptoms and associated disability [72]. In Malaysia, a study looking at pain complaints in primary care settings showed that a higher proportion of Indian patients visited government clinics, while more Chinese patients sought out private doctors for complaints of pain [132]. This difference in health care-seeking behaviour of different races may lead to differences in quality of pain relief experienced by the different ethnic groups. Cultural factors may also strongly influence the expression of pain. In some cultures such as the Chinese, expressing pain openly may be seen as a weakness and therefore patients often remain

Epidemiology in Chronic Pain, Gender and Cultural Aspects

stoic despite pain and suffering. Conversely, in other cultures such as Indians, pain and grief are expected to be expressed openly. In Malaysia, this may have led to stereotyping Indians as having a lower tolerance to pain. While this may well be true, there are no specific studies looking at the pain threshold and tolerance levels in different Asian racial groups to substantiate this belief. Indeed, the differences in pain experience among the ethnic groups, at least in part, may be explained by the differences in descending neural inhibition [18]. A study by Chung et al. [24] on cancer pain in Hong Kong Chinese showed that although the prevalence of pain was the same as that reported in Western populations, the severity of the pain tended to cluster around the lower levels (“mild pain”) compared with the Western reports. In another study, the authors found that both geographical location and cultural groups resulted in a different emphasis on the different aspects of quality of life [100]. Assimilation and acculturation into a foreign society may affect how individuals respond to pain. Those who have successfully integrated into the foreign society may be less affected by their own customs, rituals and values [76]. They tend to behave and respond in accordance with the expectations and values of their adopted society. Research with adult twins supported the views that cultural patterns of behaviour within families, and not genes, determined perceived sensibility to pain [73]. In a study of Chinese and non-Chinese Canadian infants receiving routine immunisation, it was found that significant differences in acute pain response occurred at 2 months of age with the Chinese infants showing greater response [95]. The authors concluded that cultural influences occurred well before acquisition of language. A recent UK study, however, found that acculturation only explained part but not all the differences between South

57

Asian ethnic groups (1,165 Indian, 401 Pakistani and 348 Bangladeshi) and white Europeans in the prevalence of widespread pain [88].

Summary The clinical relevance of ethnic influences on pain requires further study as it is still unclear how consistent are the differences in clinical presentations across ethnic groups. More importantly, is ethnicity associated with differential pain treatment due to the attitudes of health care professionals? Experience with chronic pain patients in Malaysia and Hong Kong showed that although they have vastly different cultural backgrounds and beliefs compared with patients from Western cultures, there is a lot of similarity in the responses of the respective patients to chronic pain, and the resulting distress and disability. Similarly, cognitive behavioural therapy-based pain management programmes that teach self-management strategies for chronic pain, although developed in the West, have been applied successfully in Malaysian and Hong Kong patients of different ethnic groups [86]. These programmes are conducted using local languages, applying cognitive behavioural therapy principles but using culturally appropriate examples and illustrations so that they are meaningful to the patients. Factors affecting the report of pain, the responses to chronic pain and its effect on work, activity and mood are multiple and influence the prevalence of chronic pain in different populations. Although gender, ethnic and cultural differences may have an impact on patients’ response, it is important to be aware that stereotypes and prejudices based on gender and ethnicity alone may influence the diagnosis and treatment offered to patients of different background.

References 1. 2.

Agreus L, Svardsudd K, Nyren O, et al. The epidemiology of abdominal symptoms: Prevalence and demographic characteristics in a Swedish adult population. Scand J Gastroenterol 1994;29:102–9. Aun C, Lam YM, Collett B. Evaluation of the use of a visual analogue scale in Chinese patients. Pain 1986;25:215– 21.

58

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38.

Mary CARDOSA, Phoon Ping CHEN

Barrero LH, Hsu YH, Terwedow H, et al. Prevalence and physical determinants of low back pain in a rural Chinese population. Spine 2006;31:2728–34. Bates MS. Biocultural Dimensions of Chronic Pain: Implications for Treatment of Multiethnic Populations. Albany, NY: State University of New York Press, 1996. Becker N, Bondegaard Thomsen A, Olsen AK, et al. Pain epidemiology and health related quality of life in chronic nonmalignant pain patients referred to a Danish multi-disciplinary pain center. Pain 1997;73:393–400. Berkley KJ. Sex differences in pain. Behav Brain Sci 1997;20:371–80. Blyth FM, March LM, Brnabic AJ, et al. Chronic pain and frequent use of health care. Pain 2004;111:51–8. Blyth FM, March LM, Brnabic AJ, et al. Chronic pain in Australia: A prevalence study. Pain 2001;89:127–34. Blyth FM, March LM, Cousins MJ. Chronic pain-related disability and use of analgesia and health services in a Sydney community. Med J Aust 2003;179:84–7. Blyth FM, March LM, Nicholas MK, et al. Chronic pain, work performance and litigation. Pain 2003;103:41–7. Borghouts JA, Koes BW, Vondeling H, et al. Cost-of-illness of neck pain in the Netherlands in 1996. Pain 1999;80:629– 36. Breitbart W, McDonald MV, Rosenfeld B, et al. Pain in ambulatory AIDS patients. Pain 1996;68:315–21. Breivik H, Collett B, Ventafridda V, et al. Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. Eur J Pain 2006;10:287–333. Buer N, Linton SJ. Fear-avoidance beliefs and catastrophizing: Occurrence and risk factors in back pain and ADL in the general population. Pain 2002;99:485–91. Burton AK, Tillotson KM, Main CJ, et al. Psychosocial predictors of outcome in acute and subacute low back trouble. Spine 1995;20:722–8. Buskila D, Sarzi-Puttini P, Ablin JN. The genetics of fibromyalgia syndrome. Pharmacogenomics 2007;8:67–74. Cairns BE. The influence of gender and sex steroids on craniofacial nociception. Headache 2007;47:319–24. Campbell CM, France CR, Robinson ME, et al. Ethnic differences in diffuse noxious inhibitory controls. J Pain 2008;9:759–66. Chapman WP, Jones CM. Variations in cutaneous and visceral pain sensitivity in normal subjects. J Clin Invest 1944;23:81. Chen PP, Chen J, Gin T, et al. Out-patient chronic pain service in Hong Kong: prospective study. Hong Kong Med J 2004;10:150–5. Chrubasik S, Junck H, Zappe HA, et al. A survey on pain complaints and health care utilization on a German population sample. Eur J Anaesthesiol 1998;15:397–408. Chung JW, Wong CH, Yang JC, et al. The construction of a pain intensity verbal rating scale in Chinese. Acta Anaesthesiol Sin 1999;37:65–71. Chung JW, Wong TK. Prevalence of pain in a community population. Pain Med 2007;8:235–42. Chung, JWY, Yang JCS, Wong TKS. The significance of pain among Chinese patients with cancer in Hong Kong. Acta Anaesthesiol Sin 1999;37:9–14. Clark R, Anderson NB, Clark VR, et al. Racism as a stressor for African-Americans. A biopsychosocial model. Am Psychol 1999;54:805–16. Cox J, Reimann F, Nicholas AK, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006;444(7121):894–8. Craft RM, Mogil JS, Aloisi AM. Sex differences in pain and analgesia: The role of gonadal hormones. Eur J Pain 2004;8:397–411. Creamer P, Lethbridge-Cejku M, Hochberg MC. Determinants of pain severity in knee osteoarthritis: Effect of demographic and psychosocial variables using three pain measures. J Rheumatol 1999;26:1785–90. Crombie IK. The potential of epidemiology. In Crombie IK, Croft PR, Linton SJ, LeResche L, Von Korff M, eds. Epidemiology of Pain. Seattle: IASP Press, 1999. Crook J, Rideout E, Browne G. The prevalence of pain complaints in a general population. Pain 1984;18:299–314. Dahan A, Kest B, Waxman AR, et al. Sex-specific responses to opiates: animal and human studies. Anesth Analg 2008;107:83–95. Dao TT, LeResche LJ. Gender differences in pain. J Orofac Pain 2000;14:169–84. Desbiens NA, Mueller-Rizner N, Connors AF Jr, et al. Pain in the oldest-old during hospitalization and up to one year later. J Am Geriatr Soc 1997;45:1167–72. Edwards CL, Fillingim RB, Keefe F. Race, ethnicity and pain. Pain 2001;94:133–7. Edwards RR. Genetic predictors of acute and chronic pain. Current Rheumatology Reports 2006;8:411–7. Edwards RR, Fillingim RB. Ethnic differences in thermal pain responses. Psychosom Med 1999;61:346–54. Edwards RR, Doleys DM, Fillingim RB, et al. Ethnic differences in pain tolerance: Clinical implications in a chronic pain population. Psychosom Med 2001;63:316–23. Elliott AM, Smith BH, Penny KI, et al. The epidemiology of chronic pain in the community. Lancet 2000;355:233– 4.

Epidemiology in Chronic Pain, Gender and Cultural Aspects

59

39. Faucett J, Gordon N, Levine J. Differences in postoperative pain severity among four ethnic groups. J Pain Symptom Manage 1994;9:383–9. 40. Ferrell BA, Ferrell BR, Rivera L. Pain in cognitively impaired nursing home patients. J Pain Symptom Manage 1995;10:591–8. 41. Fillingim RB, Gear RW. Sex differences in opioid analgesia: Clinical and experimental findings. Eur J Pain 2004;8:413–25. 42. Fillingim RB, Ness TJ. Sex-related hormonal influences on pain and analgesic responses. Neurosci Biobehav Rev 2000;24:485–501. 43. Gioiosa L, Chen X, Watkins R, et al. Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine in mice. Horm Behav 2008;53:124–30. 44. Goldberg YP, MacFarlane J, MacDonald ML. Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet 2007;71:311–9. 45. Gureje O, von Korff M, Simon GE, et al. Persistent pain and well-being: A World Health Organization Study in primary care. JAMA 1998;280:147–51. 46. Halbert CH, Armstrong K, Gandy OH, et al. Racial difference in trust in health care providers. Arch Intern Med 2006;166:896–901. 47. Hasvold T, Johnson R. Headache and neck or shoulder pain — frequent and disabling complaints in the general population. Scand J Prim Health Care 1993;11:219–24. 48. Heitkemper M, Jarrett M. Irritable bowel syndrome: does gender matter? J Psychosom Res 2008;64:583–7. 49. Helme RD, Gibson SJ. The epidemiology of pain in elderly people. Clin Geriatr Med 2001;17:417–31. 50. Jim JJ, Noponen-Hietala N, Cheung KM, et al. The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration. Spine 2005;30:2735–42. 51. Jin K, Sorock GS, Courtney TK. Prevalence of low back pain in three occupational groups in Shanghai, People’s Republic of China. J Safety Res 2004;35:23–8. 52. Jones GT, Johnson RE, Wiles NJ, et al. Predicting persistent disabling low back pain in general practice: A prospective cohort study. Br J Gen Pract 2006;56:334–41. 53. Jones GT, Macfarlane GJ. Epidemiology of pain in older persons. In Gibson SJ, Weiner DK, eds. Pain in Older Persons. Progress in Pain Research and Management, Vol. 35. Seattle: IASP Press, 2005:3–23. 54. Jordan MS, Lumley MA, Leisen JC. The relationships of cognitive coping and pain control beliefs to pain and adjustment among African-American and Caucasian women with rheumatoid arthritis. Arthrit Care Res 1998;11:80–8. 55. Kakigi R, Nakata H. Intracerebral pain processing in a Yoga master who claims not to feel pain during meditation. Eur J Pain 2005;9:581–6. 56. Kalichman L, Hunter DJ. The genetics of intervertebral disc degeneration. Familial predisposition and heritability estimation. Joint Bone Spine 2008;75:383–7. 57. Kay L, Jorgensen T, Jensen KH. Epidemiology of abdominal symptoms in a random population: Prevalence, incidence, and natural history. Eur J Epidemiol 1994;10:559–66. 58. Keefe FJ, Lefebvre JC, Egert JR, et al. The relationship of gender to pain, pain behavior, and disability in osteoarthritis patients: The role of catastrophizing. Pain 2000;87:325–34. 59. Kehlet H, Jensen TS, Woolf C. Persistent postsurgical pain: Risk factors and prevention. Lancet 2006;367:1618–25. 60. Kendall NAS, Linton SJ, Main CJ. Guide to assessing psychological yellow flags in acute low back pain: Risk factors for long-term disability and work loss. Wellington, New Zealand: Accident Rehabilitation and Compensation Insurance Corporation of New Zealand and the National Health Committee, 1997. 61. Lasch KE. Culture and pain. Pain Clinical Updates. Seattle: IASP Press, 2002:10(5). 62. Last JM, ed. Dictionary of Epidemiology, 2nd edn. New York: Oxford University Press, 1988:42. 63. Lee A, Gin T, Oh TE. Opioid requirements and responses in Asians. Anaesth Intensive Care 1997;25:665–70. 64. Lee S, Chen PP, Lee A, et al. A prospective evaluation of health related quality of life in Chinese patients with chronic non-cancer pain. Hong Kong Med J 2005;11:174–80. 65. LeResche L. Gender considerations in the epidemiology of chronic pain. In Crombie IK, Croft PR, Linton SJ, LeResche L, Von Korff M, eds. Epidemiology of Pain. Seattle: IASP Press, 1999. 66. LeResche L. Sex, gender and clinical pain. In Flor H, Kalso E, Dostrovsky JO, eds. Proceeding of the 11th World Congress on Pain. Seattle: IASP Press, 2006:543–54. 67. Levine FM, De Simone LL. The effects of experimenter gender on pain report in male and female subjects. Pain 1991;44:69–72. 68. Lilienfeld AM, Lilienfeld DE. Foundations of Epidemiology, 2nd edn. New York: Oxford University Press, 1980. 69. Linton SJ, Boersma K. Early identification of patients at risk of developing a persistent back problem: The predictive validity of the Orebro musculoskeletal pain questionnaire. Clin J Pain 2003;19:80–6. 70. Linton SJ, Hellsing AL, Hallden K. A population-based study of spinal pain among 35–45-year-old individuals. Prevalence, sick leave, and health care use. Spine 1998;23:1457–63. 71. Linton SJ, Ryberg M. Do epidemiological results replicate? The prevalence and health-economic consequences of neck and back pain in the general population. Eur J Pain 2000;4:347–54.

60

Mary CARDOSA, Phoon Ping CHEN

72. Madan I, Reading I, Palmer KT, et al. Cultural differences in musculoskeletal symptoms and disability. Int J Epidemiol 2008;37:1181–9. 73. MacGregor AJ, Griffiths GO, Baker J, et al. Determinants of pressure pain threshold in adult twins: Evidence that shared environmental influences predominate. Pain 1997;73:253–7. 74. Malmivaara A, Hakkinen U, Aro T, et al. The treatment of acute low back pain — bed rest, exercises, or ordinary activity? N Engl J Med 1995;332:351–5. 75. Maniadakis N, Gray A. The economic burden of back pain in the UK. Pain 2000;84:95–103. 76. McKenzie KJ, Crowcroft NS. Race, ethnicity, culture, and science. BMJ 1994;309:286–7. 77. McMillan AS, Wong MC, Zheng J, et al. Prevalence of orofacial pain and treatment seeking in Hong Kong Chinese. J Orofac Pain 2006;20:218–25. 78. McRoberts JA, Li J, Ennes HS, et al. Sex-dependent differences in the activity and modulation of N-methyl-d-aspartic acid receptors in rat dorsal root ganglia neurons. Neuroscience 2007;148:1015–20. 79. Meyer-Rosberg K, Kvarnström A, Kinnman E, et al. Peripheral neuropathic pain — a multidimensional burden for patients. Eur J Pain 2001;5:379–89. 80. Miu DKY, Chan TY, Chan MH. Pain and disability in a group of Chinese elderly out-patients in Hong Kong. Hong Kong Med J 2004;10:160–5. 81. Mogil JS, Yu L, Basbaum AI. Pain genes?: Natural variation and transgenic mutants. Ann Rev Neurosci 2000;23:777– 811. 82. Montagna P. Recent advances in the pharmacogenomics of pain and headache. Neurol Sci 2007; 28(Suppl 2):S208– 12. 83. Moulin DE, Clark AJ, Speechley M, et al. Chronic pain in Canada — prevalence, treatment, impact and the role of opioid analgesia. Pain Res Manage 2002;7:179–84. 84. Ng B, Dinsdale JE, Rollnik JD, et al. The effect of ethnicity on prescriptions for patient-controlled analgesia for postoperative pain. Pain 1996;66:9–12. 85. Ng KFJ, Tsui SL, Chan WS. Prevalence of common chronic pain in Hong Kong adults. Clin J Pain 2002;18:275–81. 86. Nicholas MK, Cardosa MS, Chen PP. Developing multidisciplinary cognitive behavioural pain management programs in Asia. In Flor H, Kalso E, Dostrovsky JP, eds. Proceedings of the World Congress in Pain. Seattle: IASP Press, 2006:773– 87. 87. Nilsen CV, Lande SA, Malterud K. Is headache a women’s disease? [in Swedish] Tidsskr Nor Laegeforen 1998;118:1404– 7. 88. Palmer B, Macfarlane G, Afzal C, et al. Acculturation and the prevalence of pain amongst South Asian minority ethnic groups in the UK. Rheumatology 2007;46:1009–14. 89. Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology 2000;93:1123–33. 90. Perquin CW, Hazebroek-Kampschreur AA, Hunfeld JA, et al. Pain in children and adolescents: A common experience. Pain 2000;87:51–8. 91. Poulsen L, Brøsen K, Arendt-Nielsen L, et al. Codeine and morphine in extensive and poor metabolizers of sparteine: Pharmacokinetics, analgesic effect and side effects. Eur J Clin Pharmacol 1996;51:289–95. 92. Riley JL, Robinson ME, Wise EA, et al. Sex differences in the perception of noxious experimental stimuli: A metaanalysis. Pain 1998;74:181–7. 93. Riley JL, Wade JB, Myers CD, et al. Racial/ethnic differences in the experience of chronic pain. Pain 2002;100:291– 8. 94. Robinson ME, Gagnon CM, Riley 3rd JL, et al. Altering gender role expectations: Effects on pain tolerance, pain threshold, and pain ratings. J Pain 2003;4:284–8. 95. Rosmus C, Johnston CC, Chan-Yip A, et al. Pain response in Chinese and non-Chinese Canadian infants: Is there a difference? Soc Sci Med 2000;51:175–84. 96. Roth-Isigkeit A, Thyen U, Stoven H, et al. Pain among children and adolescents: Restriction in daily living and triggering factors. Pediatrics 2005;115:152–62. 97. Rustoen T, Wahl AK, Hanestad BR, et al. Prevalence and characteristics of chronic pain in the general Norwegian population. Eur J Pain 2004;8:555–65. 98. Sartain JB, Barry JJ. The impact of an acute pain service on postoperative pain management. Anaesth Intensive Care 1999;27:375–80. 99. Scher AI, Stewart WF, Lipton RB. Migraine and headache: A meta-analytical approach. In Crombie IK, Croft PR, Linton SJ, LeResche L, Von Korff M. Epidemiology of Pain. Seattle: IASP Press, 1999. 100. Scott NW, Fayers PM, Aaronson NK, et al. The relationship between overall quality of life and its subdimensions was influenced by culture: analysis of an international database. J Clin Epidemiol 2008;61:788–95. 101. Selim AJ, Fincke G, Ren XS, et al. Racial differences in the use of lumbar spine radiographs: Results from the veterans health study. Spine 2001;26:1364–9.

Epidemiology in Chronic Pain, Gender and Cultural Aspects

61

102. Sheffield D, Kirby DS, Biles PL, et al. Comparison of perception of angina pectoris during exercise testing in AfricanAmericans versus Caucasians. Am J Cardiol 1999;83:106–8, A8 103. Sheffield D, Biles PL, Orom H, et al. Race and sex differences in cutaneous pain perception. Psychosom Med 2000:62:517– 23. 104. Siddall PJ, Cousins MJ. Persistent pain as a disease entity: Implications for clinical management. Anesth Analg 2004;99:510–20. 105. Smedley BD, Stith AY, Nelson AR, eds. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. Washington DC: National Academies Press, 2003. 106. Smith BH, Elliott AM, Chambers WA, et al. The impact of chronic pain in the community. Fam Pract 2001;18:292– 9. 107. Smith BH, Torrance N, Bennett MI, et al. Health and quality of life associated with chronic pain of predominantly neuropathic origin in the community. Clin J Pain 2007;23:143–9. 108. Soetanto AL, Chung JW, Wong TK. Are there gender differences in pain perception? J Neurosci Nurs 2006;38:172–6. 109. Soetanto AL, Chung JW, Wong TK. Gender differences in pain perception: A signal detection theory approach. Acta Anaesthesiol Sin 2004;42:15–22. 110. Streltzer J, Wade TC. The influence of cultural group on the under-treatment of postoperative pain. Psychosom Med 1981;43:397–403. 111. Sutton-Tyrrell K. Assessing bias in case-controlled studies. Stroke 1991;22:938–42. 112. Tan EC, Lim Y, Teo YY, et al. Ethnic differences in pain perception and patient-controlled analgesia usage for postoperative pain. J Pain 2008;9:849–55. 113. Thomas E, Peat G, Harris L, et al. The prevalence of pain and pain interference in a general population of older adults: Cross-sectional findings from the North Staffordshire Osteoarthritis Project (NorStOP). Pain 2004;110:361–8. 114. Todd KH, Deaton C, D’Adamo AP, et al. Ethnicity and analgesic practice. Ann Emerg Med 2000;35:11–6. 115. Todd KH, Lee T, Hoffman JR. The effect of ethnicity on physician estimates of pain severity in patients with isolated extremity trauma. JAMA 1994;271:925–8. 116. Torrance N, Smith BH, Bennett MI, et al. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain 2006;7:281–9. 117. Tsai YF. Gender differences in pain and depressive tendency among Chinese elders with knee osteoarthritis Pain 2007;130(1-2):188–94. 118. Tsui SL, Lo RJ, Tong WN, et al. A clinical audit for postoperative pain control on 1,443 surgical patients. Acta Anaesthesiol Sin 1995;33:137–48. 119. Unruh AM. Gender variations in clinical pain experience. Pain 1996; 65:123–67. 120. Unruh AM, Ritchie J, Merskey H. Does gender affect appraisal of pain and pain coping strategies? Clin J Pain 1999;15:31–40. 121. US Census Bureau, International Database. Global population profile 2002, http://www.census.gov/ipc/www/wp02. html. 122. van Den Kerkhof EG, Hopman WM, Towheed TE, et al. for Canadian Multicentre Osteoporosis Study Research Group. The impact of sampling and measurement on the prevalence of self-reported pain in Canada. Pain Res Manag 2003;8:157–63. 123. van Leeuwen MT, Blyth FM, March LM, et al. Chronic pain and reduced work effectiveness: The hidden cost to Australian employers. Eur J Pain 2006;10:161–6. 124. Veerapen K, Wigley RD, Valkenburg H. Musculoskeletal pain in Malaysia: A COPCORD survey. J Rheumatol 2007;34:207–13. 125. Verhaak PF, Kerssens JJ, Dekker J, et al. Prevalence of chronic benign pain disorder among adults: A review of the literature. Pain 1998;77:231–9. 126. Weisse CS, Sorum PC, Sanders KN, et al. Do gender and race affect decisions about pain management. J Gen Intern Med 2001;16:211–7. 127. White SF, Asher, MA, et al. Patients’ perceptions of overall function, pain, and appearance after primary posterior instrumentation and fusion for idiopathic scoliosis. Spine 1999;24:1693–9. 128. Wiesenfeld-Hallin Z. Sex differences in pain perception. Gend Med 2005;2:137–45. 129. Wolfe F, Ross K, Anderson J,et al. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995;38(1):19–28. 130. Wood AJ, Zhou HH. Ethnic differences in drug disposition and responsiveness. Clin Pharmacokinet 1991;20:350–73. 131. Yunus MB. Gender differences in fibromyalgia and other related syndromes. J Gend Specif Med 2002;5:42–7. 132. Zalinawati AH, Teng CL, Kamil MA, et al. Pain morbidity in primary care. Med J Malaysia 2006;61:162–7. 133. Zhang Y, Sun Z, Liu J, et al. Advances in susceptibility genetics of intervertebral degenerative disc disease. Int J Biol Sci 2008;4:283–90.

6

Jacqueline YAP, Tony GIN

Biostatistics in Pain Medicine INTRODUCTION Special features of the study of pain EVIDENCE-BASED MEDICINE IN PAIN MEDICINE Levels of evidence Systematic reviews and metaanalysis Presentation of results from metaanalysis Application of evidence-based medicine in pain medicine CLINICAL TRIALS IN PAIN RESEARCH General principles Randomisation Control group Participant selection Blinding Sample size Outcome measurement Analysis Presentation of results Limitations of randomised controlled trials OUTCOME MEASUREMENT AND QUESTIONNAIRES IN STUDIES OF PAIN Reliability Validity Responsiveness Issues in outcome measurement for clinical trials in pain research CONCLUSION REFERENCES

Introduction The objective of this chapter is to increase the understanding of evidence-based medicine and clinical trials as applied to pain medicine. Practical concerns specific to pain medicine will be addressed and some guidance will be provided for the interpretation of results. Full details of statistical analysis are not within the scope of the chapter since there are numerous resources such as textbooks in biostatistics that are readily available.

Special features of the study of pain The experience of pain is a biopsychosocial phenomenon. Thus, a traditional biological approach is often not sufficient for research studies in the field of pain medicine. This fact affects the methodology, assessment and interpretation of results of research in acute and chronic pain. For example, in the context of pain assessment, many factors other than a patient’s experience of pain could potentially influence the report of pain. Such factors include other subjective experiences and feelings (e.g. anxiety), and motivational factors (e.g. appearing stoic). Outcome measures that are important in pain studies include not only pain measures but also measures of physical and emotional functioning because common psychosocial factors (e.g. sleep disturbance, anger, depression) will exert an influence on a patient’s response. It is also well known that reported changes in pain do not always match behaviour and function. Fordyce et al. [15] found that positive patient statements about severity of chronic pain and functional impairment after an intervention showed few correlations with medication consumption, health care utilisation, or recorded activity level. It has been suggested that the analysis of patient behaviour should also be included in the evaluation of chronic pain.

64

Jacqueline YAP, Tony GIN

Finally, not all pain is the same. One needs to be aware that acute pain is not a single entity. For example, the efficacy of different analgesic agents varies according to the acute pain model and severity of the noxious stimuli. There are significant differences between acute and chronic pain in terms of quality, duration and mechanism. Studies of acute and chronic pain must be designed differently. For example, unlike acute pain, the measurement of pain has not been subject to standardisation in chronic pain. This is because standardisation may not be possible across all chronic pain conditions, which are often heterogeneous in terms of patient groups, mechanism and type of pain. In addition, the ethics of using placebo controls in chronic pain have been debated. In single dose analgesic studies in acute pain, there are rarely ethical objections to the use of placebos, because patients understand that they can terminate the study and take additional analgesics at any time. Chronic pain studies are a different matter. Although a placebo control has been considered appropriate in studies of chronic pain syndromes in patients who have already failed all standard treatments, chronic administration of a placebo cannot be justified in pain syndromes that generally respond to therapy.

Evidence-Based Medicine in Pain Medicine Evidence-based medicine (EBM) has been described as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients” [35]. Large amounts of information currently exist in the medical literature. Evidence-based medicine can be utilised to distil this information and assist the clinician to use this knowledge with wisdom. Resources for EBM relevant to pain medicine include: • Cochrane Pain, Palliative and Supportive Care Group (http://www.cochrane.org/index.htm) • Bandolier (http://www.jr2.ox.ac.uk/ Bandolier/index.html) • The Oxford Pain Internet Site (http://www. jr2.ox.ac.uk/bandolier/booth/painpag/) • The Centre for Evidence Based Medicine (http://www.cebm.net/) • Database — MEDLINE, EMBASE, PsychINFO, Cochrane Central Register of Controlled Trials (CENTRAL) • Journals — Bandolier Journal, Pain, Clinical Journal of Pain, Pain Medicine and other painrelated journals.

Although EBM is popular, it does have potentially significant and persistent problems [18, 25]. It is interesting to note there is no evidence that the practice of EBM as originally defined improves patient outcome, and EBM recommendations may turn out to be incorrect at times. EBM is not a new paradigm, and many physicians were practising medicine based on available evidence before the advent of EBM. A pragmatic appraisal of EBM is that it can provide good evidence with the assistance of modern information technology, but it must be carefully interpreted by experts and individuals before it can be applied to patients.

Levels of evidence The strength of evidence can be presented according to various classifications. A typical classification in descending order of credibility is: • Strong evidence from at least one systematic review of multiple well-designed randomised controlled trials • Strong evidence from at least one properly designed randomised controlled trial of appropriate size • Evidence from well-designed trials such as non-randomised trials, cohort studies, time series or matched case-controlled studies • Ev i d e n c e f r o m w e l l - d e s i g n e d n o n experimental studies from more than one centre or research group • Opinions of respected authorities, based on clinical evidence, descriptive studies, or reports of expert committees.

Systematic reviews and metaanalysis A systematic review is a summary of the medical literature that uses explicit methods to perform a thorough literature search, critically appraises individual studies and employs appropriate statistical techniques to combine valid results. A meta-analysis is basically the quantitative statistical methods to combine and summarise the results from independent studies. It also assesses the presence and effect of heterogeneity, and explores the robustness of the results using sensitivity analysis.

The process of systematic reviews and metaanalysis The process of systematic review involves the following steps:

Biostatistics in Pain Medicine

1. Define the question The intervention of interest, relevant patient groups and outcomes should be clearly stated. 2. Literature search Published and unpublished literature from English and non-English sources, studies reported at conferences, expert opinions should be sought and identified. Publication bias is of concern here. For example, studies that report positive outcomes are more likely to be reported in journals than negative studies. Although the negative studies may eventually be published, there can be a delay of several years and it can take this long before a systematic review reports an accurate estimate of the treatment effect. 3. Study appraisal Each study identified will then be reviewed and critically appraised for quality and eligibility to be included into the systematic review. This process should involve two independent reviewers. There is no mandatory provision for an expert in the field to assess the relevance of the studies for inclusion or exclusion, but this should be a crucial step because studies may be methodologically perfect for inclusion yet flawed in the way they try to answer the question posed. 4. Pooling of results Once the individual studies have been assessed to be eligible for inclusion into the systematic review, the findings from each study need to be combined to produce an overall conclusion. Qualitative and quantitative techniques may be used to pool the results. Further information on these techniques is discussed in the next section on presentation of results. 5. Discussion Issues such as heterogeneity of the studies, bias and the applicability of the findings should be addressed.

Limitations of systematic reviews and metaanalysis Meta-analysis extracts additional information through calculation from existing data. Hence, the findings from a meta-analysis need to be validated with the results from subsequent large-scale, wellconducted randomised controlled trials. In general, there has been agreement between meta-analysis and subsequent large-scale high quality trials but discrepancies also exist [24]. A comparison by Ioanndis and colleagues found that the results of subsequent large trials have disagreed with conclusions from a systematic review and meta-

65

analysis 10–23% of the time [22]. In view of this limitation, the results of a meta-analysis should not be considered as additional evidence over the original raw data. Systematic reviews have replaced traditional narrative reviews in summarising research evidence. Some deficiencies of narrative reviews are overcome by applying the same rigorous standards to secondary research (where the unit of study is other research studies) as should be applied to primary research (the original empirical study). During the literature search, selection bias is of concern in any systematic review or metaanalysis. Funnel plots can be used to assess the likely presence of selection bias. The effect size of the studies is compared against the sample size in a funnel plot. In the absence of bias, the plot should resemble an inverted symmetrical funnel as smaller studies have more chance of variability and will scatter more widely at the bottom of the graph. If selection bias exists, then there will be an asymmetrical appearance of the funnel plot with a gap at the bottom of the funnel. Finally, systematic reviews are not all equal, and quality issues are important. There is clear guidance on the process of developing systematic reviews [8, 11]. A recommendation on the reporting of systematic reviews is provided by the Quality of Reporting of Meta-analysis (QUOROM) statement in an effort to improve the quality of systematic reviews [29]. Another major concern in meta-analysis is the extent to which different studies are combined. In order to get a precise answer in a meta-analysis, only studies that match exactly should be included. Unfortunately, research differs in conditions such as patient group, setting, intervention and outcome. Hence, heterogeneity is constantly present in a meta-analysis. One then needs to ascertain whether it will significantly affect the conclusion of the meta-analysis. In order to be more transparent with heterogeneity, its presence can be more explicitly shown by a graphical or tabled presentation of the results from individual studies, grouped by important variables such as patient and intervention. Statistical tests of heterogeneity exist but may lack power, so that while positive results suggest that there may be a problem, a negative result does not exclude heterogeneity [16].

66

Jacqueline YAP, Tony GIN

Sensitivity analysis explores the robustness of the results of the meta-analysis by varying the approach to combining the studies. The effect of excluding various categories of studies and the consistency of the results across different subgroups may be explored. If sensitivity analysis is not performed, the results of the meta-analysis should be interpreted with caution as consistency is not guaranteed. In a meta-analysis, common data from different studies are combined while others are discarded. For example, meta-analysis of pain relief typically uses 50% reduction in pain as a dichotomous outcome. This results in the information on the exact amount of pain relieved being lost, as the result is classified into successes and failures. This problem may affect the applicability of the meta-analysis. Loss of information may also occur as a result of inadequate presentation of results. A pooled number needed to treat (NNT) may be the only result presented by a meta-analysis, but the NNT changes significantly with a change in baseline risk.

Presentation of results from meta-analysis Data from a meta-analysis are displayed by pictorial representations and summary measures of the effect (Fig. 6.01).

Pictorial representation L’Abbé Plot

Figure 6.01 An idealised L’Abbé Plot [4]. Copyright permission granted from Bandolier (http://www. jr2.ox.ac.uk/bandolier/booth/glossary/labbe.html).

are represented as a circle or square (the measured effect), with a horizontal line (the 95% confidence interval) around the main finding. The size of the circle or square may vary to reflect the amount of information (or weighting) in that individual study. The width of the horizontal line or 95% confidence interval represents the uncertainty of the estimate of treatment effect for that study, hence a narrower width implies greater precision. The overall size and direction of the effect is displayed at the bottom of the figure together with the statistical significance.

The proportion of patients achieving the outcome with the experimental intervention is plotted (Y axis) against the proportion achieving the outcome in the control (X axis). Each point on the L’Abbé Plot is one trial in a systematic review. Trials in which the experimental treatment is better than the control will lie in the upper left of the plot between the Y axis and the line of equality. If the points are mainly focused on the line of equality, then there is no difference between the intervention and control. The L’Abbé Plot also gives a quick indication of the heterogeneity and the level of agreement among trials. Points representing a consistent cloud imply a homogenous effect. But if the points are scattered all over the graph, and particularly if they cross the line of equality, then this is an indication of heterogeneity and the reader should be cautious when interpreting the results.

Summary measure of effect The treatment effect can be summarised and presented in different ways depending on the type of data available. Sometimes this is a difference in the mean or median, or in the case of data that are binary, this may be a difference in proportions, risk, odds or number needed to treat. Table 6.01 represents the results of a hypothetical pain trial with summary measures derived from the results.

The summary measure used in the Forest Plot is usually the odds ratio. The scale is a logarithmic scale. The line of equality is where the odds ratio equals 1. The findings from each individual study

Risks The risk (or probability) is the likelihood of an event happening. If the event in the paracetamol group is 90 and its non-event is 10, then the risk

Biostatistics in Pain Medicine

Figure 6.02

67

Hypothetical Forest Plot.

is 90/(90+10)=0.9 or 90%. If the risk had doubled (relative risk=2) or halved (relative risk=0.5), then the event would be twice as likely, or half as likely to occur. The relative risk (RR) is the risk of an event in the treated group divided by the risk of an event in the control group, i.e. the ratio of EER to CER. It is usually expressed as a decimal proportion. If the risks in the two groups are the same, then the relative risk is 1. Referring to the example in Table 6.01, a RR=1.8 means that the event in the treatment group is 1.8 times more likely to occur when compared with those in the control group. Relative risks are interpretated and used as follows; • A RR greater than 1 means that the treatment effect is better than placebo. • If the 95% confidence interval of a RR does not include 1, then the result is statistically significant. If the 95% confidence interval of a RR includes 1, then the result is not statistically significant. • The RR is frequently reported in prospective cohort studies, meta-analysis and can also be used as a summary measure in clinical trials. In these study designs, it is advisable to measure the relative risk rather than the odds ratio as it is easier to intuitively interpret the relative risk. However, in retrospective case control studies, it is not possible to calculate the relative risk since subjects are chosen based

on the presence or absence of the disease. In addition, the incidence rate and risk cannot be determined because accurate information about the total number of patients at risk is not available. In this situation, one may approximate the relative risk using the odds ratio if the event is rare when compared with the total. The relative risk reduction (RRR) is the proportion of the risk removed by the treatment. It is the absolute risk reduction (ARR) divided by the initial risk in control group, i.e. (EER-CER)/CER. It is usually expressed as a percentage. Relative risk measures do not reflect the baseline risk of individuals with regard to the outcome being measured. Therefore, relative risk measures cannot discriminate between large and small effects, and do not give a true reflection of how much benefit the individual would derive from the intervention. Relative risk measures tend to overestimate the benefits of an intervention and for this reason are popular with the health industries. The absolute risk reduction (ARR) is the absolute change in risk, where the effect is due solely the treatment and nothing else. It is the risk of an event in the treatment group minus the risk of an event in the control group (EER-CER). It is usually expressed as a percentage.

68

Jacqueline YAP, Tony GIN

Table 6.01

Results of a hypothetical acute pain trial

Treatment

Number who achieved at least 50% pain relief

Number who did not achieve at least 50% pain relief

Total number of patients treated

Paracetamol 1 g

90

10

100

Placebo

50

50

100

Summary measures: Experimental event rate (EER)

90/100=0.90 or 90%

Control event rate (CER)

50/100=0.50 or 50%

Relative risk (EER/CER)

0.9/0.5=1.8

Relative risk reduction ((EER-CER)/CER)

((0.9–0.5)/0.5)=0.8 or 80%

Absolute risk reduction (EER-CER)

0.9–0.5=0.4 or 40%

Experimental event odds

90/10=9

Control event odds

50/50=1

Odds ratio

9/1=9

NNT (1/ARR)

1/0.4=2.5

Absolute risk measures overcome the problems of relative risk measures because they reflect the baseline risk and are better at discriminating between small and large treatment effects. However, since absolute risk measures are dependent on the baseline risk, they have limited generalisability. Hence, it is inappropriate to extrapolate published absolute risk reductions from one population to another population with different baseline risks. While relative and absolute risk can show that an intervention works compared with the control, they are of limited use in informing clinicians how well an intervention works (i.e. the magnitude of the effect). The NNT is a summary measure that provides this information.

Odds The odds are the ratio of events to non-events. For example, if the event in the paracetamol group is 90 and its non-event rate is 10, then the experimental event odds are 90/10=9. The odds ratio (OR) is the odds of an event in the treated group divided by the odds of an event in the control group. It is usually expressed as a decimal proportion. Odds ratios are not usually as intuitively interpreted by clinicians as relative risks.

Odds ratios are interpretated and used as follows; • An OR that is greater than 1 means that the experimental intervention is better than control. • If a 95% confidence interval is calculated, statistical significance is assumed if the interval does not include 1. • Despite the difficulty in interpreting the odds ratio, it is useful in a few specific situations. In retrospective case control studies where the relative risk cannot be directly calculated, the odds ratio approximates the relative risk when the event is rare. In addition, logistic regression models work in terms of odds and its coefficients are reported as odds ratios.

Number needed to treat (NNT) The NNT is the number of people who have to be treated to achieve the desired outcome in one person. When interpreting the NNT, it is always treatment specific, relative to the comparator, and applies to a particular outcome and duration of treatment. For example, if the NNT=3 for an analgesic, this means that for every three patients given the active treatment over a certain duration when compared with the control, one patient experienced the desired outcome. The NNT has clinical relevance because it shows immediately the

Biostatistics in Pain Medicine

clinical effect and effort required to produce one result with a particular intervention. The NNT can be calculated by a number of ways, such as by using the absolute risk reduction (ARR), a table of odds ratios with corresponding NNTs [34], or a nomogram of NNT based on the relative risk reduction [9]. The commonest method would be to use the absolute risk reduction, i.e. NNT is 1/ARR or 1/(EER-CER). In other words, NNT =

1 (IMPact/TOTact) - (IMPcon/TOTcon)

where IMPact = number of patients given active treatment achieving target TOTact = total number of patients given active treatment IMPcon = number of patients given control treatment achieving target TOTcon = total number of patients given control treatment An NNT=1 means that a favourable outcome occurs in every patient given the treatment but in no patient in the control group. This “perfect result” is very difficult to achieve in the clinical setting. Hence, NNTs of 2 or 3 are generally accepted as an indication of an effective treatment. Higher NNTs represent less effective outcomes from a treatment. A negative NNT occurs when there are more favourable events with the control than with the treatment. The concept of NNT can also be applied to harm. The number needed to harm (NNH) should be high because it implies that adverse events are rare. It must be reinforced that the interpretation of NNTs are by definition relative. There is no rule that says that an NNT of 2 is always good and one of 100 is always bad: it depends on the context. For example, a NNT of 20 in a fatal condition could be regarded as reasonable — one person in 20 could be saved. The same NNT would not be regarded in the same manner in a different context, such as for the prevention of postoperative vomiting if the treatment is associated with significant adverse effects. In addition, low values of NNH are not desirable because this means adverse events are

69

common, but this is influenced by the severity of the adverse event. For example, one may accept a lower NNH for a mild adverse event when the treatment is very effective. The benefits of NNT include; • Provides a single numerical reminder of effectiveness. • Gives a measure of the therapeutic effort required to obtain one beneficial event. • NNTs are better at discriminating between large and small treatment effects and more useful than relative risk measures in describing outcomes in clinical trials. • NNTs are useful in comparing the utility of treatments in comparable trials with comparable outcomes. NNT league tables (e.g. Oxford league table of analgesic efficacy) can rank treatments relative to one another and may be helpful in making a choice of treatment based on the comparative effectiveness. However, NNT also has its limitations and they include the followings; • Calculation of the NNT requires dichotomous data. • The comparison of NNTs across a disease condition can only be done if conditions, outcomes and interventions are similar. For example, most of the NNTs published in analgesic league tables relate to the acute pain setting, with a single drug dose and assessment over a 6-hour period. These league tables should not be used to make treatment decisions for patients with chronic pain who require repeated and continuous treatment. • The NNT is sensitive to trials with high CER, i.e. the proportion of patients in the control group that achieved the outcome. Increases in CER results in a higher NNT result and hence, apparently, less effective NNTs . This can be easily worked out from the formula NNT=1/(EER-CER). • NNTs for a specified intervention in an individual patient depend not only on the nature of the treatment but also on the baseline risk. If a patient’s expected event rate is high, then he will benefit more. • The NNT is only a part of any patient assessment — one should also consider other factors including the consequences of the disease, costs, availability of alternative

70

Jacqueline YAP, Tony GIN

treatments, side effects of the treatment and patient preferences. In summary, the NNT is a very useful summary measure because its interpretation is clinically intuitive. However, one should be aware that NNTs are tools which need to be used wisely.

Application of evidenced-based medicine in pain medicine In pain medicine, factors that have driven the use of EBM include the: • Presence of marked variations in management in clinical practice • Increasing cost of health care due to the rapid development of new medical technology. On the other hand, factors that have hindered the application of EBM are the: • Relative paucity of randomised controlled trials in pain management • Extensive spread of pain literature across medical and surgical subspecialties and basic science.

Issues to be considered when implementing EBM Individual baseline risk.- the effect of an intervention may vary because patients do not share the same morbidity or risk. For any given measurement of treatment effectiveness, patients at higher risk will generally experience greater levels of absolute risk reduction or impact from a treatment. Threshold for implementation. – the evidence of effectiveness alone does not imply that an intervention should be accepted. The implementation of an intervention depends on whether the benefit is sufficiently large relative to the risks and costs, and other issues such as equity and willingness to take risks. These differences explain the variations in decisions made when the same evidence is presented to different people. One approach to the decision about whether an intervention should be implemented is to determine a threshold above which treatment would be offered. This threshold might be expressed in terms of cost effectiveness ratios that define the cost of achieving a unit of benefit below which an intervention is seen as worth implementing. When evaluating the evidence, different decision makers will use different criteria to prioritise treatments

for implementation. Policymakers may emphasise societal gains in health and efficiency, while clinicians may consider the well-being of their patients to be most important. Knowledge gaps - one should bear in mind that the existence of knowledge gaps between medical science and medical practice in pain medicine has made the application of EBM in this field difficult. In practice, this void is filled by “clinical judgment” and “clinical experience”. In such situations, clinicians should not only utilise available EBM tools but also analyse resources from patients (e.g. pain diaries) thus accommodating treatment according to the patient. Epistemological considerations - finally, the degree to which clinicians adopt good quality research into practice will be influenced by the extent to whether the results conflict with their own professional experience and beliefs. This reflects an epistemological mismatch between the evidence that researchers produce and the evidence that practising clinicians value [6, 28].

Clinical Trials in Pain Research General principles The single most important step in designing a trial is to clearly and specifically define the research question to be answered. This may seem relatively straight forward, but challenges may influence the trial design (e.g. requirement for very large sample size or ethical concerns). The second step in designing a trial is to clearly specify the primary outcome to be assessed. After that, it should be logical to determine the appropriate measurement tools and methods of analysis. The primary outcome measure should be specified before the data are collected or analysed because otherwise there is the risk that the methodology will be inadequate and the results insufficient to answer the question posed.

Randomisation Randomisation aims to reduce the effect of confounding variables and to eliminate selection bias in trials. When randomisation is implemented

Biostatistics in Pain Medicine

correctly and when sufficient numbers of participants are enrolled, the distributions of all potential confounding variables are likely to be equal across groups. True randomisation requires both a valid means of generating random assignment and a mechanism to preserve the integrity of random assignment. In a systematic review on the effectiveness of transcutaneous electrical nerve stimulation (TENS) in acute postoperative pain by Carroll and colleagues [7], 17 studies were regarded as randomised controlled trials in acute postoperative pain. The authors concluded from these randomised trials that there was no benefit of TENS compared with placebo. Of the excluded trials, 19 were not randomised controlled trials and among these trials, it was concluded that TENS had a positive analgesic effect. This review showed that non-randomised studies overestimated treatment effects.

Control group Placebo controlled trials A placebo is an inactive substance or treatment. The placebo effect is defined as the “response of a subject to a substance or to any procedure known to be without any therapeutic effect for the specific condition being treated” [5]. Though the extent of the placebo effect has been questioned, it appears to be real and of large magnitude in studies of pain [21]. The placebo effect is conventionally assessed by using placebo controlled trials. However, recent literature has suggested an alternative approach using hidden and open administration of study treatment, which has the advantage of assessing the placebo effect in studies without placebo conditions in addition to providing information on the magnitude of the placebo effect [2, 33].

Benefits of placebo control • Allows the specific efficacy of the new intervention to be distinguished from the placebo effect. The magnitude of the nonspecific effect in a study can be estimated by the mean (or median) response in the placebo control group. Assuming a simple additive model of treatment effects, the placebo group response can be subtracted from the response of the active treatment group to estimate the specific efficacy of the active intervention. • Allows double-blinding in a trial, thereby avoiding biases that might occur if patients or

71

investigators knew who was receiving which treatment. For example, it would have been impossible to blind participants or evaluators if one group received a treatment and the other did not. Bias is more likely to occur in trials using no-treatment controls than those using placebo controls.

Limitations of placebo control • Placebo controlled trials do not always answer a clinically relevant question. Practising clinicians, who have several analgesics available to be used clinically, may not want to know whether another analgesic works better than nothing, but rather, how the new analgesic compares with existing standards of care. • Ethical issues related to placebo controls remain unanswered. Although a placebo control has been considered to be appropriate in situations where patients have failed all standard treatment, it is difficult to justify the chronic administration of a placebo in pain syndromes that generally respond to a known therapy. In this situation, an investigator may consider giving both placebo and active treatment groups access to a standard analgesic “rescue” dose. Here, the “rescue” analgesic then becomes another important outcome measure. The other alternative may be to give both placebo and active treatment as an addon treatment where all patients are already on optimal doses of standard treatment. The ethics of placebo controlled trials is further discussed in Chapter 7. No-treatment controlled trials There are two primary situations in which it may be important to include a control group of participants who receive no intervention. • When it is critical to determine the overall efficacy of a new treatment, but there are practical and/or ethical problems with using a placebo or sham control. • When the goal of a trial is to assess the magnitude of a placebo effect. To measure the placebo effect properly requires the comparison of patients receiving placebo with those receiving no treatment at all. Here, the placebo response needs to be distinguished from the effects of regression to the mean. Regression to the mean classically occurs in medical conditions with fluctuating

72

Jacqueline YAP, Tony GIN

symptoms. In this situation, subjects who have enrolled in a clinical trial when their disease is in a worse period will have a natural tendency to improve during the progression of the trial. The inclusion of a “no-treatment group” in addition to a placebo group may differentiate the placebo response from regression to the mean. The improvement in the no-treatment group may then be attributed to regression to the mean, and the additional improvement in the placebo group is the placebo response.

Non-inferiority and equivalence trials Given the ethical concerns about placebo controlled trials and the inability of no-treatment groups to maintain blinding, investigators may decide to show that a new drug is either “no worse than” (a non-inferiority trial) or “as good as” (an equivalence trial) a treatment that is commonly accepted as effective. These trials are standard in evaluating medications for conditions where the risks of placebo assignment are widely regarded as too great (e.g. thrombolytic agents for acute myocardial infarction). However, these trials are presently not considered as standard in pain management because the risks of temporarily forgoing the active treatment are not as obvious. In addition, there are potential problems with interpreting such studies: • Demonstrating no significant differences between two analgesics does not prove that they are equivalent. These trials require much larger sample sizes, because equivalence or non-inferiority must be documented within relatively narrow margins. The lack of significant differences may be a result of inadequate power if the sample size is too small. • Demonstrating that two treatments are the same does not show either of them worked. These trials assume that the standard therapy would have been superior to placebo had a placebo arm been included.

Participant selection There are two conflicting priorities in the selection of participants. Ensuring homogeneity among participants in a trial permits greater confidence that the observed outcomes are a result of the treatment and limits the variability that might obscure the results. This approach increases the internal validity of the study, but limits the generalisability of the results. On the other hand,

enrolling a heterogeneous group of subjects is more likely to reflect all those who could potentially benefit from the intervention and allows detection of potential variations in a treatment’s efficacy among higher and lower risk patients. The external validity or generalisability of the study will be increased. However, this approach can substantially increase the sample required to ensure that the trial has adequate statistical power.

Blinding A goal of clinical trials is to design the experiment such that any observed changes in outcome are caused specifically by the treatment being studied. Moore has shown that studies in medicine can be biased as a result of the structure of a trial [31]. For example, non-randomised and unblinded studies overestimated treatment effects by 40% and 17% respectively. Blinding may be single (participant blinded) or double (investigator and participant blinded). Double blinding is preferable.

Participant blinding Participants in all groups must believe they are getting the real treatment. If the control group believes they are getting the placebo treatment, which may be a less effective intervention, the trial may spuriously reveal a benefit in the active treatment group. Participant blinding may be difficult to maintain where there is an obvious treatment effect or side effect. In addition to creating appropriate placebos, investigators should validate that the blinding was preserved by asking participants the treatment they believe they received. If the blinding was successful, this result should be consistent with random allocation. Investigator blinding Blinding of outcome assessors is critical to minimise the chance that evaluators will more favourably rate those known to be receiving the active treatment, impart different levels of enthusiasm, or prescribe different co-interventions to patients in different groups.

Sample size The statistical power of a trial is the probability of detecting a treatment difference when one truly exists. Researchers traditionally consider a study to be adequately powered if it has at least an 80% chance of detecting an effect when one exists (i.e.

Biostatistics in Pain Medicine

beta or type II error ≤ 0.2). However, one should be aware that this value is arbitrary. In practice, the power of a trial is decided by considering both the sample size that can reasonably be enrolled, and the relative importance of limiting false negative conclusions (type II error) versus false positive conclusions (type I error). There are various methods to work out the sample size for different study designs and these may involve formulae, sample size tables [26], and computer programs such as PASS [19]. An alternative approach to presenting sample size considerations is to calculate the size of the effect that would need to be present to produce a statistically significant outcome. Although this approach is not recommended, it remains in common use. For example, Cohen’s d Effect Size is often used for sample size calculation, but one should be aware that this is a poor substitute for the investigator who avoids committing to an estimate of the clinically important difference that should be detected between interventions. An often used standard formula for sample size calculation for comparison of two means is: N = σ2ƒ( α , β ) Δ2 where N = number of patients in each treatment group σ = standard deviation of the primary outcome measure ƒ( α , β ) = alpha and beta error Δ = difference to be detected between treatment effects Investigators usually accept the conventional α and β errors, thus the main influence that they have over sample size is their choice of Δ. Hopefully, the treatment effect will be at least as large as Δ. In addition, it is important to minimise all errors that may increase the σ2 or variance of the treatment effect in the study. A large variance will make it more difficult to detect a difference, even if one truly exists.

Increasing the likelihood of detecting the difference between treatment effects The investigator has to decide the minimum difference that he or she would like to detect. A larger minimum difference requires a smaller sample size. This may be achieved by maximising

73

the dose, intensity of treatment or baseline risk of subjects.

Decreasing the variability in outcome measurement An improvement in the precision of an outcome measurement will allow a reduction in sample size. For example, Jensen & McFarland have suggested that the variation in pain intensity over the course of a week may introduce a large amount of variability [23]. It was shown that this error can be decreased by averaging daily pain measures over a week. Adjusting for covariates with significant effects on the primary outcome If one is aware of the covariates or confounding variables that have significant effects on the outcome, it is advisable to exclude these variables from the study. If it is not possible to do so, then these variables will need to be adjusted using statistical techniques such as regression analysis. Study designs Some investigators have suggested crossover designs, enriched enrolment designs, and n-of 1 designs to increase power and reduce sample size. However, these designs have their respective disadvantages inherent to the architecture and requirements of the trial design [27].

Outcome measurement Measures of pain can be unidimensional or multidimensional. Unidimensional measures of pain include pain relief scales such as the visual analogue scale, categorical scale and numerical rating scale. Multidimensional measures (e.g. McGill Pain Questionnaire) provide additional information about the characteristics of the pain and its impact. Most measures of pain are based on subjective self-report. Self-report measures can be influenced by a variety of factors such as mood and sleep disturbance. Multiple outcome measures are required to adequately capture the complexity of the pain experience and how it can be modified by pain management interventions. Although there are no objective measures of pain, associated factors such as hyperalgesia (e.g. mechanical withdrawal threshold) or functional impairment (e.g. ambulation) may provide additional information.

74

Jacqueline YAP, Tony GIN

Table 6.02

Core outcome domains in chronic pain trials [39]

• • • •

Pain Physical functioning Emotional functioning Participants’ ratings of improvement and satisfaction with treatment • Symptoms and adverse events • Participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Copyright permission granted from Copyright Clearance Center’s Rightslink/Elsevier Limited.

Analgesic requirement is also commonly used as a surrogate measure of pain. So, how do we evaluate pain, and what is considered a successful or non-successful outcome, bearing in mind that pain is a multidimensional subjective phenomenon? In 2003, under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), specialists from academia, governmental agencies and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered by investigators in chronic pain clinical trials (Table 6.02) [39]. Investigators are recommended to assess outcomes representing six core domains as shown in the table below. This landmark guideline was followed by further recommendations by IMMPACT on the core outcome measures for chronic pain trials (Table 6.03) [12]. Criteria used to assess potential outcome measures include the appropriateness of the measure’s content and conceptual model, reliability, validity, responsiveness, acceptability, feasibility, availability, equivalence of different methods of administration, and translations for different cultures and languages. It is important to acknowledge that wide disagreement exists on the choice of the best outcome measure. The recommendations by IMMPACT are meant to be outcome measurements to be considered in chronic pain clinical trials. These recommendations are not meant to be a compulsory requirement for publication in scientific journals or to imply that positive outcomes for all these outcome measures must be obtained to judge if a treatment is effective.

Some of the dispute can be explained by the differences in the questions that are being studied and the data that can be practically collected. Please refer to the next main section for further discussion regarding the statistical requirements of outcome measurement tools in pain studies and Chapter 4 for further information on pain evaluation.

Analysis Different analytic approaches may be possible depending on the type of data available, the trial structure and the different questions that need to be answered. Specific statistical tests and analyses are readily covered in statistical textbooks and will not be discussed in detail in this chapter. However, there are some concepts in relation to the interpretation of the results that are essential, and these will be discussed below.

Table 6.03

•

•

•

•

•

•

Core outcome measures in chronic pain trials [12]

Pain: 11-point (0–10) numerical rating scale of pain intensity Categorical rating of pain intensity (none, mild, moderate, severe) in circumstances in which numerical ratings may be problematic Use of rescue analgesics Physical functioning (either one of two measures): Multidimensional Pain Inventory Interference Scale Brief Pain Inventory interference items Emotional functioning (at least one of two measures): Beck Depression Inventory Profile of Mood States Participant ratings of global improvement and satisfaction with treatment: Patient Global Impression of Change Symptoms and adverse events: Passive capture of spontaneously reported adverse events and symptoms and use of openended prompts Participant disposition: Detailed information regarding participant recruitment and progress through the trial, including all information specified in the CONSORT guidelines [30].

Copyright permission granted from Copyright Clearance Center’s Rightslink/Elsevier Limited.

Biostatistics in Pain Medicine

Statistical significance versus Clinical significance The p-value indicates the probability of obtaining a value for the test statistic at least as extreme as the one observed, assuming that the null hypothesis is true. A p-value of 0.05 is conventionally used to signify statistical significance. This convention implies that one has a 5% chance of incorrectly rejecting the null hypothesis. It is important to be aware that a number of factors can contribute to a statistical significance. One could get a statistically “significant” result when the effect is very large (despite having only a small sample) or if the sample is very large (even if the actual effect is small). As the sample size increases, the test statistic necessary to achieve a conventional level of statistical significance decreases. For example, if there are 30 subjects in a study, a Pearson correlation coefficient of 0.10 may not be statistically significant. However, if the sample size is 200, a Pearson correlation of 0.10 could be statistically significant at p 10/minute.

of indomethacin and diclofenac (Table 9.08). The limitations of NSAIDs are their efficacy and side effects. Unlike opioids, NSAIDs have a ceiling analgesic effect [45]. NSAIDs are less popular now as their efficacy, when combine with opioid, is not superior to a paracetamol/opioid regimen. Paracetamol is much less ulcerogenic to the gastrointestinal tract than NSAIDs.

For advanced cancers, suitable dosage adjustment is necessary since the pre-terminal patient may be somnolent and have major organ failure and be unable to tolerate a high dose of opioid.

Other groups of drugs for cancer pain management (Table 9.09)

• •

Non-steroidal anti-inflammatory drugs and paracetamol Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are useful in cancer pain management because of their analgesic effect (especially) in bone pain related to malignancy [45, 81]. For mild pain, paracetamol or an NSAID alone is often sufficient. For more severe pain, this group of drugs can be given in addition to opioids. The side effects of NSAIDs/paracetamol are not the same as opioids. Administration of the former allows a lower dosage of the latter (opioidsparing effect) resulting in less opioid-related side effects. It is recommended in the WHO’s analgesic ladder for the use of NSAIDs with other drugs in the control of cancer pain (see above). In order to control cancer pain effectively, it is desirable to choose an NSAID that is potent and relatively long acting with minimal side effects. Commonly used NSAIDs include diclofenac, ketoprofen, ibruprofen, sulindac and suppository preparations

Table 9.08 Common NSAIDs/paracetamol prescriptions for cancer pain control Ketoprofen SR

100 mg

qd to q12h

Diclofenac SR

100 mg

qd to q12h

Sulindac

100–200 mg

q12h

Indomethacin suppository

100 mg

q12h

Naproxen

250–500 mg

q12h

Paracetamol

500–1000 mg

q6h

Note: dose adjustment is essential especially in the elderly or patients with impaired hepatic or renal functions.

Cancer pain is complex involving multiple mechanisms. It is common to have nocigenic as well as neuropathic components in a patient with cancer pain [138]. The former pain component responds well to opioid and NSAIDs; neuropathic components require other groups of drugs for effective analgesia. For clinical features of neuropathic pain, please refer to Chapter 23 for details. Tricyclic antidepressants (TCAs) [110] and anticonvulsants are effective in controlling neuropathic pain [9]. The analgesic effect of TCAs is independent of their antidepressant effect and the dose range for the former effect is also lower than the latter. The commonest prescribed TCA for treatment of neuropathic pain is amitriptyline [9]. Apart from its analgesic properties, amitriptyline causes sedation, which may be helpful for the cancer patient who is also an insomniac. However, caution against urinary retention must be taken in elderly male patients. Anticonvulsants [82] and local anaesthetics [66] are useful for the spasmodic, shooting type of neuropathic pain. Anticonvulsants exert their analgesic effect mainly through modulation of voltage-gated sodium channels, calcium channels or by enhancing the gamma aminobutyric acid (GABA), inhibitory system [43]. The anticonvulsant carbamazepine (Tegretol) is commonly used for trigeminal neuralgia and neuropathic pain [111, 129]. Gabapentin is a structural analogue of GABA, initially introduced as an anticonvulsant in 1994. Its analgesic effect was soon discovered and this drug is gaining popularity in pain medicine due to its good analgesic efficacy, tolerability, and relatively fewer side effects and drug interactions. The mechanism of its analgesic action is likely to be an inhibitory effect on presynaptic calcium influx through inhibition on voltage-gated calcium channels containing alpha-2-delta-1 subunit [120]. Clinically, gabapentin is particularly effective

Cancer Pain 145

in treating neuropathic pain with allodynia, spontaneous, paroxysmal, lancinating and steadyburning characteristics [76]. Its effectiveness in treating neuropathic pain related to cancer has been substantiated [14, 113]. Pregabalin is a newer member of this group of analgesics. Its onset of action is much faster than gabapentin. Gamma aminobutyric acid agonists like benzodiazepines are also very useful in cancer pain management. This group of drugs can be used as sedative and hypnotics as the patient is likely to be suffering sleep loss due to pain. Diazepam, lorazepam and midazolam are commonly used benzodiazepines for patients with cancer pain. In addition, drugs like baclofen (GABAb) are particularly useful for treating pain due to muscle spasm [147]. Ketamine is an NMDA antagonist which is useful in pain resistant to morphine, especially with a neuropathic element [130]. Ketamine can be given IV at 0.1 to 0.5 mg/kg and used as an adjunct to opioid therapy. Other routes of ketamine are by subcutaneous, oral, extradural and intrathecal administration. However, ketamine is also associated with significant side effects including nausea, sedation, dry mouth and hallucination [85]. Bisphosphonates are useful in the treatment of pain related to bone metastases. This group of drugs is particularly effective in those malignancies associated with marked osteolysis such as multiple myeloma and metastatic breast cancer. Bisphosphonates act by exerting an inhibitory action on osteoclastic activity on bone. This activitity is stimulated by factors secreted by malignant cells and is believed to cause pain. Bisphosphonates are commonly given to control bone pain, lower elevated plasma calcium and delay pathological fractures due to malignancy [150]. Generally, this group of drugs is safe; the most important side effect is the rapid lowering of calcium when the drug is administered rapidly in patients with widespread osteoclastic activity. The American Society of Clinical Oncology (ASCO) clinical practice guidelines recommend a regimen for treatment of bone pain due to metastatic tumour: disodium pamidronate (Aredia), a second generation bisphosphonate, 90 mg can be infused intravenously over 2 hours, repeated every 3 to 4 weeks [4]. Third generation bisphosphonates like zoledronic acid are more potent and can be infused in a much shorter time than pamidronate [112]. The ASCO guidelines recommend intravenous

Table 9.09 Other useful drugs for cancer pain

control 1. Tricyclic antidepressants (a) amitriptyline (b) nortriptyline (c) doxepin 2. Membrane stabilisers (a) Anticonvulsants • carbamazepine • valproic acid • gabapentin • pregabalin (b) Sodium channel blockers • lignocaine • mexiletine 3. Benzodiazepines: hypnotics, sedatives (a) GABAa agonist • diazepam • clonazepam (b) GABAb agonist • baclofen 4. Bisphosphonates 5. Other drugs (a) Alpha 2 agonist • clonidine • dexmedetermidine (b) NMDA antagonist • ketamine

infusion of zoledronic acid 4 mg over 15 minutes, repeated every 3 to 4 weeks, for malignant bone pain [4].

Importance of analgesic coverage when switching from one regimen to another In cases of unsatisfactory analgesia or other reasons requiring a change to the analgesic regimen, it is essential to provide adequate coverage during the switching-over period. One method is to prescribe a transdermal fentanyl patch to the patient whose pain is not well controlled with oral morphine. Fentanyl needs at least 8 hours to achieve a sufficient plasma level [91]. Time is required for the release of drug from the patch preparation, the formation of a skin depot, subsequent absorption into the blood and access to opioid receptors. If the oral morphine is withdrawn abruptly, there may be a period of insufficient opioid coverage when the patient will suffer greater pain or even opioid withdrawal symptoms. It is important to either

146 Siu Lun TSUI, Chi Wai CHEUNG

prescribe a rescue analgesic (morphine syrup or injection) and/or tail down the old regimen drug gradually so as to provide a smooth transition to the new regimen.

Neuraxial Analgesia

success rate in pain relief [31, 52, 84]. Other disadvantages of the extradural route include more fibrosis around the catheter, pain on injection and a higher incidence of catheter blockage. However, since the drugs are deposited outside the dura mater, the extradural route allows more flexibility in the choice of drug.

Overview

Spinal drug delivery systems

Neuraxial analgesia is the administration of analgesic drugs at the spinal column (intrathecal or extradural route) or into the ventricles of the brain. The discovery of endogenous opioid receptors in 1971 and their locations in the central nervous system led to research and development of a new approach to manage pain. Wang first reported the use of intrathecal morphine on a patient suffering from cancer pain in 1979 [143]. The neuraxial administration of opioid and other drugs is an important means of treating malignant as well as non-malignant pain. The mechanism of spinal opioid analgesia involves the administration of opioids in the extradural or intrathecal space, in close proximity to the endogenous opioid receptors. These receptors are found abundantly in the spinal grey matter especially at the substantia gelatinosa. Opioid agonists act on these receptors presynaptically at the primary afferent neurons as well as postsynaptically at the second order neurons to inhibit pain transmission. In contrast to systemic opioid administration, the analgesic dose ranges of extradural and intrathecal opioids are as low as 1/10th to 1/100th respectively [84]. Spinal opioid achieves a much better quality of analgesia and the side effects of systemic opioid can be minimised. Unlike neurolytic procedures, neuraxial analgesia is reversible and produces more widespread analgesia; it is particularly effective in cancer pain that occurs bilaterally or at multiple sites. Please also refer to Chapter 28 for more details on this analgesic technique.

The administration of spinal opioid alone or in combination with local anaesthetics, α2 adrenergic agonists or other drugs can be achieved through different delivery systems. The choice of the drug delivery system depends on the life expectancy of the patient, degree of care available to top-up the drug and the cost.

Extradural versus intrathecal routes Comparing the extradural and intrathecal routes, the former requires a larger dose of opioid (10 times) and the onset is also delayed. With high dosages, a significant systemic absorption may occur and result in significant systemic side effects. The intrathecal route is associated with a higher

Waldman and Coombs classified six types of spinal drug delivery systems [142]. The type I system involves a catheter that is inserted traditionally without subcutaneous tunnelling. It is simple, but has the highest risk of infection and is only suitable for short- term use (up to 1 week). This method is commonly employed as a temporary catheter for testing the effectiveness of spinal analgesia before implantation of a longterm catheter. Also, a temporary spinal catheter allows excellent analgesia to fill the gap before anti-cancer therapy becomes effective. The type II system involves subcutaneous tunnelling of the spinal catheter. It is more resistant to spinal canal infection and can be used for a longer period of up to a month. This system is useful for patients with short life expectancy and suffering from intractable pain. A high degree of aseptic care is required to manage type I and type II spinal catheter systems since the injection port is exteriorised. However, these catheters are less expensive and simpler for insertion. Totally implantable systems, type III to VI, are feasible for home care because their risk of infection is much less. The type III system includes a totally implanted subcutaneous injection port so that drugs can be given through intermittent percutaneous injections. Commercially available silicon domes are resistant to multiple punctures by atraumatic Huber needles for up to 1,000 times. In order to minimise multiple punctures, an alternative is to administer the drug, intermittently or by continuous infusion, though a catheter and bacterial filter system connected to a Huber needle. The latter is inserted percutaneously to the injection

Cancer Pain 147

port. The needle can be changed at regular intervals of several days to a week. Types III to IV systems involve implanting a drug reservoir (usually with capacity of 50 ml). This drug reservoir allows topping-up at much longer intervals so as to further minimise infection and trauma to the injection port. The type IV system is a patient-controlled system (e.g. AlgoMed System of Medtronic). In a similar way to a PCA device, the patient presses an implanted, manually activated pumping chamber to deliver a 1-ml dose of drug through the catheter. Subsequent filling of the empty chamber from the implanted drug reservoir takes an hour, so that a lockout interval mechanism is incorporated to avoid inadvertent overdose. Type V and VI systems allow continuous infusion through a totally implanted pump to provide a constant analgesic level at the CNS. Type VI is the most sophisticated system in that programming of the pump is allowed through a telemetry system. The choice of spinal drug delivery system depends on the life expectancy of the patient, cost affordability as well as logistical support of the institution and patient’s family. Generally speaking, the sophisticated totally implantable system (IV to VI) is not feasible or cost effective if the patient has a life expectancy of less than three months [60, 67].

Choice of neuraxial medication In carefully selected patients, initial good pain relief is usually achieved with spinal opioid. Preservativefree morphine is the commonest drug used. The efficacy of spinal morphine is best in continuous somatic or visceral pain. Its analgesic efficacy is less satisfactory (in descending order) in neuropathic pain, incident pain due to movement, visceral pain due to intestinal obstruction and pain of open ulcer [84]. Even with an initial good response, it is not uncommon that analgesia becomes less satisfactory with time. The most important causes of dose escalation are drug tolerance, the development of new pain as the tumour further progresses and metastases, or mechanisms that develop as elaborated earlier in this chapter. Metastases to the epidural space were found in about 70% of patients with refractory pain during intrathecal analgesia [84]. As with systemic opioids, tolerance to spinal opioid develops with time so that a larger dose is needed to achieve the same degree of analgesia.

Apart from drug tolerance, it is well known that nerve involvement is common in cancer and the resulting neuropathic pain is less responsive to opioid. In cases of unsatisfactory analgesia despite rapid opioid dose escalation, other drugs should be tried. Local anaesthetic and α2 adrenergic agonists like clonidine are particularly useful in such circumstances. The addition of bupivacaine to opioid regains analgesia in 90% of cancer pain patients who were refractory to extradural opioid alone [84]. Local anaesthetic is particularly useful in substituting opioids to provide a “drug holiday” to reset the tolerant opioid receptors, so that a lower dose can be recommenced later. Local anaesthetic also blocks involuntary reflexes and spasms that aggravate pain. It has been demonstrated that the addition of bupivacaine to morphine in intrathecal mixtures resulted in a diminished progression of dose escalation of the morphine [139]. However, spinal (especially intrathecal) administration of local anaesthetic results in blocking touch, sympathetic as well as motor functions. This may lead to hypotension, urinary retention and lower limb weakness. Extreme caution is mandatory to ensure adequate hydration and monitoring of motor power when local anaesthetic is used. In general, a low dose of intrathecal local anaesthetic (bupivacaine M

M>F

F>M

Age of onset

20–40 years, 25% before 10 years

Late 20s

Any age

Site of pain

Retro-orbital, frontotemporal, may radiate to occiput and neck

Area of trigeminal innervation, periorbital

Bifrontal, bioccipital

Side of pain

Typically unilateral, can be bilateral

Strictly unilateral

Bilateral

Character of pain

throbbing

Non-throbbing, excruciating, penetrating

Dull, non-throbbing, constriction-band like

Pain duration

4–72 hours

15 min to 3 hours

30 min to 7 days

Pain frequency

Single attacks with periods of freedom

Daily or several times a day during cluster period

No definite pattern, 2 days a week Not >2 days a week

50–100 mg PO, up to 300 mg/24 hours 6 mg SC, up to 12 mg/24 hours

Qd–bd, not >2 days a week.

Ergotamine

1–2 mg PO at onset 1 mg suppository

Max 3 doses per attack or day Not to exceed 2 days a week and 10 mg per week

Dihydroergotamine

0.25–1 mg IM/IV/SC, may be repeated q1h

Max 3 mg/24 hours Not >20 ampoules per month

12–20 mg IV, 16 mg IM 1.5mg PO bd 20 mg qid 4 mg

For 2 days For 2 days 21 tablets over 6 days

NSAID • Acetylsalicylic Acid (mild attacks) • Acetaminophen (mild attacks) • Naproxen • Ketorolac • Ibuprofen • Indomethacin Opioids • Codeine • Pethidine • Butorphanol Sumatriptan

Steroids • Dexamethasone • Prednisone • Methylprednisolone Miscellaneous • Chlorpromazine

• Midrin (isometheptene 65 mg, dichloraphenazone 100 mg, acetaminophen 325 mg) or Midrid • Fiorinal (butalbital with aspirin and caffeine)

Max 120 mg/day Max 2.4 g/day Max 200 mg/day

Max 4 doses/day, not >2days a week

Qd–bd, not >2 days a week.

50 mg IM 0.1 mg/kg IV infusion over 20 mins, repeated after 15 mins 2 tablets stat and then 1 tablet q1h

Max 37.5 mg IV

1–2 tablets q4h

Max 6 tablets per day, not >2 days a week

Max 5 tablets per day, not >2 days a week

PO = per oral.

must be taught the proper use of drugs. Overuse of medications, including analgesics, ergotamine and possibly sumatriptan, can lead to drug tolerance and rebound headache (analgesic rebound) on abrupt withdrawal [84]. Use of abortive drugs should be limited when possible to two days a week.

Abortive treatment Abortive treatment is the mainstay of therapy and ranges from simple analgesics, strong opioids, specific 5HT1 agonists and adjuvants such as prokinetics, antiemetics and anxiolytics. Prompt treatment is

166 Chi Tim HUNG, Steven H.S. WONG

Table 10.07

Drugs for prophylactic treatment of migraine

Drug

Dose and route

Beta-blockers • Atenolol • Metoprolol • Nadolol • Propranolol

50–150 mg/day PO 100–200 mg/day PO 20–120 mg/day PO 60–120 mg/day PO

Calcium channel blockers • Verapamil • Flunarizine

120–480 mg/day PO 5–10 mg/day PO

Anticonvulsants • Sodium valproate • Gabapentin • Topiramate

500–1500 mg/day 1800–2400 mg/day 100–200 mg/day

Antidepressants • Amitriptyline • Nortriptyline • Dothepin • Fluoxetine (SSRI)

10–100 mg/day PO 10–100 mg/day PO 10–120 mg /day PO 20–80 mg/day

NSAID • Naproxen • Indomethacin

250–500 mg/day PO 25–200 mg/day PO

Cyproheptadine

4–16 mg/day

Methysergide

2 mg PO nocte, gradually to tds, usually 4–8 mg/day

Monoamine oxidase inhibitors • Phenelzine

Remarks

Not > 1 week per month Not > 1 week per month

Resting period needed

15–60 mg/day PO

PO = per oral.

critical in aborting an attack [92]. Special attention has to be paid to the route of administration of these drugs. For patients with severe nausea and vomiting or headache of rapid onset, the oral absorption of drugs may not be reliable or effective. The parenteral route, nasal or rectal routes have to be explored. Rest in a dark and quiet environment during the early part of headache may help to decrease the duration of the attack [5]. Despite the importance of pharmacotherapy, not every migraine attack requires all the use of powerful drugs with their potential attendant side effects. It is logical to adopt a stepwise or algorithmic approach according to the severity of the migraine [92]. A guideline on the management strategy will be helpful [76]. For mild attacks of short duration (1oC, demonstrated on at least two separate occasions) [64], or by testing of sudomotor function, both at rest and evoked. Trophic changes can be demonstrated on plain radiography as patchy demineralisation, or abnormal radionuclide uptake on bone scintigraphy. A three-phase Technetium (99mTc) scanning is the most commonly employed bone scintigraphy technique. The delayed threephase scans showing diffuse regional uptake are especially useful, having over 80% sensitivity and specificity for CRPS [33]. The major differential diagnoses for CRPS are listed in Table 15.05 [52]. A trial sympathetic block only serves to test whether the condition is sympathetically maintained and is not necessary in the diagnosis of CRPS. However, these blocks can provide useful information about the probable efficacy of certain treatment modalities, which will be discussed below. The pathophysiology of CRPS is not clearly understood. There is a strong general suspicion that CRPS involves some pathophysiological process in the central nervous system, with or without concomitant changes in the peripheral nervous system [29]. The central process involved is most likely central sensitisation via NMDA and tachykinin-mediated actions on spinal neurons [93, 94]. The initial stimulus for and maintenance of this sensitisation can result from ongoing Cafferent input, augmented by postganglionic

Table 15.05 Differential diagnoses for CRPS 1. CRPS (I from II or vice versa) 2. Unrecognised local pathology — fracture, sprain, strain 3. Traumatic vasospasm 4. Cellulitis 5. Raynaud’s disease 6. Thromboangiitis obliterans 7. Paget’s disease

sympathetic neurons in the case of sympathetically maintained pain. This result includes threshold reduction, increased responsiveness, recruitment of novel inputs and widening of receptive fields in dorsal horn neurons [14, 74, 91]. In addition to these neurological processes, CRPS also seems to have a significant inflammatory element in its pathogenesis. For instance, there is accumulation of immunoglobulins and changes in oxygen extraction in the affected area [31] which is compatible with an inflammatory process. The sympathetic element in those instances of CRPS which are sympathetically maintained are generally believed to be related to up-regulation of alpha1-receptors peripherally. Sympathetic-nociceptor ephapses and increased activity in nociceptive afferents travelling with sympathetic efferents may also contribute. Complex regional pain syndrome is a difficult condition to treat. Reasons for this difficulty are threefold. First, the pathophysiological processes of CRPS are highly complicated involving multiple mechanisms and poorly understood. Second, there is a paucity of well-designed, large-scale clinical trials in this area. Many treatment modalities are based on a trial-and-error basis or on small-scale studies or anecdotal reports. Third, there is usually a prominent psychological and socioeconomical element in the patient’s problem. It should be emphasised that the objective of management of CRPS, as in the case of many other chronic pain conditions, is not just analgesia. Early exploration of psychological factors in the disease process, minimising the “sick role”, reducing anxiety in general, identification of “secondary gains”, and counselling family members, close friends and relatives are all integral aspects of the treatment programme. Rehabilitation and restoration of function is as important as analgesia itself, and the two will usually be complimentary to each other. The use of invasive or surgical treatment, such as neurodestructive procedures, implantation of neurostimulatory devices, or amputation of body parts, should be reduced to a minimum. None of these treatments has been shown to offer any benefit; moreover, they are likely to be counterproductive in terms of the psychological rehabilitation of CRPS patients. Early physical therapy does have an important role in the management of CRPS. Physiotherapy

246 Kwok Fu Jacobus NG

directed at improving mobilisation, such as exercise programmes, stress-loading, passive movement and pool therapy, can all be helpful. These programmes will be significantly facilitated by provision of effective analgesia. Positive pressure treatments for oedema, lymphatic drainage and cooling are other treatment options [28]. Transcutaneous electrical nerve stimulation is non-invasive, simple to use and inexpensive, and should be offered for a trial in all patients, especially children. It is sometimes highly effective. However, some patient’s pain can occasionally be aggravated by TENS. In addition to psychological and physical therapies, the first-line treatment in CRPS is still pharmacological. Unfortunately, a recent review of clinical trials showed that oral corticosteroid is the only treatment to have demonstrated analgesia consistently [41]. The usual starting dose is prednisolone 30–60 mg per day orally, gradually tapering off over weeks [9, 12]. Corticosteroids should be used with caution in children. The inflammatory response certainly plays an important role in the pathogenesis of CRPS, as other antiinflammatory treatments have recently also been found to be useful. This includes topical treatment with the free radical scavenger dimethylsulfoxide [63, 95], and the systemic administration of COX2 inhibitors [25]. Intranasal and subcutaneous calcitonin, initially intended to treat the osteoporotic changes of CRPS, have also be reported to provide some analgesia [27], but there are also reports of contradictory findings. Bisphosphonates, such as alendronate or pamidronate, have recently been found to be useful in CRPS. Bisphosphonates may be administered orally over 6 to 8 weeks [48] or by daily intravenous administration for a few days [1, 83]. The mechanism by which bisphosphonates produce pain relief in CRPS remains unclear. Other drugs such as antidepressants, anticonvulsants, NSAIDs, nifedipine and clonidine can only be recommended on a trial-and-error basis, and their benefit must be carefully weighed against their numerous side effects. Should a combination of physical, psychological and oral drug therapies prove unsatisfactory, sympathetic blockade and other nerve blocks may be tried. The use of opioids is highly controversial and the response is also unpredictable. If patients do respond, the

Table 15.06 Intravenous regional block and systemic sympathetic block in CRPS [41] Technique

Drug and dose recommended

IVRB

Notes: 1. Add drug to 30–50 ml 0.5% lignocaine 2. Use smaller dose for upper limb, larger dose for lower limb Guanethidine 10–30 mg Bretylium 1–1.5 mg/kg Reserpine 1.25 mg

Systemic block

Phenoxybenzamine 40–120 mg/day oral Phentolamine 25–35 mg IV over 30 minutes

only sensible role of opioid may be in providing analgesia cover for the initiation of a mobilisation physiotherapy programme. Long-term opioid treatment is not appropriate. Sympathetic blockade can be performed in three ways. First, a sympathetic ganglion can be blocked, such as the stellate ganglion for upper limb involvement and a lumbar sympathetic block for lower limb involvement. Second, an intravenous regional block (IVRB) can be performed using various drugs, including guanethidine, bretylium and reserpine, together with local anaesthetic. Third, a systemic block can be tried with oral phenoxybenzamine or intravenous phentolamine (Table 15.06). As discussed above, not all CRPSs are sympathetically maintained, so the response to a sympathetic block is consequently highly variable. In fact, the response to a sympathetic block is the method used to evaluate the presence or absence of a sympathetic element in a patient with CRPS. If patients are found to respond favourably, then usually a series of blocks will be performed with some lasting benefit. Epidural local anaesthetic infusion can sometimes significantly reduce the pain in CRPS. This technique can be used for in-patients to provide a more favourable condition for physical therapies. Epidural opioids and clonidine may or may not be effective. Implantation of pumps is usually not warranted. In patients who do not respond to oral medications and intravenous regional treatment, another

Neuropathic Pain 247

option is to perform spinal cord stimulation[80]. The details of this technique, its advantages and limitations are discussed in more detail in Chapter 29.

Central pain Central pain is defined as regional pain caused by a primary lesion or dysfunction in the central nervous system, usually associated with abnormal sensibility to temperature and to noxious stimulation. The distribution of pain in a patient with central pain correlates anatomically with the location of the lesion in the brain or spinal cord. Therefore, the region of pain may be all or most of one side of the body, all parts of the body caudal to a level, or both extremities on one side. It may also be restricted to just one extremity or one particular part of the body. Sometimes the distribution suggests the diagnosis, for example a cheiro-oral distribution (perioral region and ipsilateral hand) is characteristic of thalamic pain. Central pain is only a collective term. There are various pain syndromes named after either the location of the lesion or the underlying disease that belong to the category of central pain. Some examples include thalamic pain, post-stroke pain and pain due to multiple sclerosis. Central pain is not an uncommon problem. The incidence is around 10–30% after spinal cord

Table 15.07

Causes of central pain

Systemic disease Multiple sclerosis Diabetes mellitus AIDS Spinal cord lesions Trauma including surgery and irradiation Vascular lesions Syringomyelia Neoplasms Myelitis Subacute combined degeneration Cerebral and thalamic lesions Stroke Trauma including surgery and irradiation Vascular lesion — arteriovenous malformations and aneurysms Neoplasms — primary and metastatic Brain abscess

injury and 25–80% in patients with multiple sclerosis. The many causes of central pain are listed in Table 15.07. In most patients with central pain, the pain will persist unless the underlying lesion is corrected. The pain is usually a great physical and psychological burden to patients, frequently rendering them physically and socially handicapped. Central pain is characterised by a complex quality of pain, usually involving a description such as burning or lancinating. There is frequently allodynia and uncomfortable paraesthesias. Hyperpathia is common in thalamic pain. The pain is usually spontaneous and continuous. It can be exacerbated by touch, heat, cold or movement. The pain can also be augmented by startling stimuli (e.g. sudden sound or light), by visceral activity (e.g. micturition) or by anxiety and emotional arousal. Associated neurological symptoms and signs are common. These may include hemiparesis, paraparesis and sensory impairment [45]. The diagnosis of central pain is further supported by the presence of a history of neurological disorder or evidence of such on computed tomography or magnetic resonance imaging. The major differential diagnoses include nociceptive pain, peripheral neuropathic pain and psychiatric cause of pain. Central pain is basically a “deafferentation pain”. Damage to the spinothalamocortical pathway is the common feature in any central pain syndrome. This damage may induce painful processes in the central nervous system and disinhibition of nociceptive neurons in the thalamus may be an important process. Transcutaneous electrical nerve stimulation may be useful in some patients with central pain. As with cases of CRPS, TENS may aggravate the pain in some patients. Most patients with central pain require some pharmacological treatment. Antidepressants such as amitriptyline, nortriptyline and clomipramine are the first-line treatment. Anticonvulsants such as gabapentin, lamotrigine or carbamazepine can be tried next if antidepressants provide inadequate relief [45, 55, 62, 85]. There are anecdotal reports of a satisfactory response to mexiletine, propranolol, anticholinesterase inhibitors, chlorpromazine, 5hydroxytryptophan and even a brief intravenous infusion of naloxone. These may be tried if the

248 Kwok Fu Jacobus NG

pain has proved refractory. Some patients will respond to opioids, at least partially. The decision to use opioids should be made after careful evaluation of the patient’s underlying disorder and psychological status, and on the merits of the individual patient. More invasive procedures are sometimes used to control refractory central pain. These include dorsal root entry zone lesion in patients with spinal cord pain and deep brain stimulation. These techniques are discussed in more detail in Chapter 30.

•

•

•

Summary • •

• •

Neuropathic pain is defined as “Pain initiated or caused by a primary lesion or dysfunction in the nervous system” Common symptoms in patients with neuropathic pain include shooting pain, burning pain, lancinating pain, allodynia and hyperalgesia; the pain can be spontaneous or evoked Neuropathic pain is commonly found in chronic pain patients The pathophysiological mechanisms of

•

• •

neuropathic pain include ectopic nerve impulse generation, cross excitation, nociceptor sensitisation, release of nociceptor input and central sensitisation The mainstay of treatment in neuropathic pain is systemic analgesics, supplemented by nerve blocks and neurodestructive procedures in selected patients Postherpetic neuralgia is a common neuropathic pain in the elderly. Management options include topical local anaesthetics and systemic analgesics, particularly with amitriptyline and the gabapentinoids Phantom pain can occur in amputees. Its major differential diagnosis is stump pain. Management options include oral analgesics and intravenous calcitonin infusion There are two types of complex regional pain syndromes (CRPS), CRPS I is not associated with nerve injury and CRPS II is associated with nerve injury The diagnosis of CRPS may not be straightforward; repeated assessment may be required to establish the diagnosis No treatment has been found to be consistently effective for CRPS. A combination of physical, pharmacological and psychological therapy seems to be most promising.

References Adami S, Fossaluzza V, Gatti D, et al. Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis 1997;56:201–4. 2. Ahn DK, Chae JM, Choi HS, et al. Central cyclo-oxygenase inhibitors reduced IL-1beta-induced hyperalgesia in temporomandibular joint of freely moving rats. Pain 2005;117:204–13. 3. Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: A randomized controlled trial. JAMA 1998;280:1831–6. 4. Bading H, Ginty DD, Greenberg ME. Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. Science 1993;260:181–6. 5. Barclay J, Patel S, Dorn G, et al. Functional down-regulation of P2X3 receptor subunit in rat sensory neurons reveals a significant role in chronic neuropathic and inflammatory pain. J Neurosci 2002;22:8139–47. 6. Bates RE Jr, Stewart CM. Atypical odontalgia: Phantom tooth pain. Oral Surg Oral Med Oral Pathol 1991;72:479–83. 7. Bernstein JE, Korman NJ, Bickers DR, et al. Topical capsaicin treatment of chronic postherpetic neuralgia. J Am Acad Dermatol 1989;21:265–70. 8. Bone M, Critchley P, Buggy DJ. Gabapentin in postamputation phantom limb pain: A randomized, double-blind, placebo-controlled, cross-over study. Reg Anesth Pain Med 2002;27:481–6. 9. Braus DF, Krauss JK, Strobel J. The shoulder-hand syndrome after stroke: A prospective clinical trial. Ann Neurol 1994;36:728–33. 10. Burke D. Microneurography, impulse conduction, and paresthesias. Muscle Nerve 1993;16:1025–32. 11. Chi SI, Levine JD, Basbaum AI. Peripheral and central contributions to the persistent expression of spinal cord fos-like immunoreactivity produced by sciatic nerve transection in the rat. Brain Res 1993;617:225–37. 1.

Neuropathic Pain 249

12. Christensen K, Jensen EM, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand 1982;148:653–5. 13. Cline MA, Ochoa J, Torebjork HE. Chronic hyperalgesia and skin warming caused by sensitized C nociceptors. Brain 1989;112(Pt 3):621–47. 14. Cook AJ, Woolf CJ, Wall PD, et al. Dynamic receptive field plasticity in rat spinal cord dorsal horn following Cprimary afferent input. Nature 1987;325:151–3. 15. Davies M, Brophy S, Williams R, et al. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care 2006;29:1518–22. 16. Davis JB, Gray J, Gunthorpe MJ, et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 2000;405:183–7. 17. Davis MP, Walsh D. Epidemiology of cancer pain and factors influencing poor pain control. Am J Hosp Palliat Care 2004;21:137–42. 18. DeBenedittis G, Besana F, Lorenzetti A. A new topical treatment for acute herpetic neuralgia and post-herpetic neuralgia: The aspirin/diethyl ether mixture. An open-label study plus a double-blind controlled clinical trial. Pain 1992;48:383–90. 19. Dellemijn PL, Vanneste JA. Randomised double-blind active-placebo-controlled crossover trial of intravenous fentanyl in neuropathic pain. Lancet 1997;349:753–8. 20. Devor M. Neuropathic pain and injured nerve: Peripheral mechanisms. Br Med Bull 1991;47:619–30. 21. Devor M, Govrin-Lippmann R, Angelides K. Na+ channel immunolocalization in peripheral mammalian axons and changes following nerve injury and neuroma formation. J Neurosci 1993;13:1976–92. 22. Dworkin RH, Corbin AE, Young JP Jr, et al. Pregabalin for the treatment of postherpetic neuralgia: A randomized, placebo-controlled trial. Neurology 2003;60:1274–83. 23. Field J, Warwick D, Bannister GC, et al. Long-term prognosis of displaced Colles’ fracture: A 10-year prospective review. Injury 1992;23:529–32. 24. Forrest JB. The response to epidural steroid injections in chronic dorsal root pain. Can Anaesth Soc J 1980;27:40–6. 25. Frade LC, Lauretti GR, Lima IC, et al. The antinociceptive effect of local or systemic parecoxib combined with lidocaine/clonidine intravenous regional analgesia for complex regional pain syndrome type I in the arm. Anesth Analg 2005;101:807–11. 26. Freynhagen R, Strojek K, Griesing T, et al. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pain 2005;115:254–63. 27. Gobelet C, Meier JL, Schaffner W, et al. Calcitonin and reflex sympathetic dystrophy syndrome. Clin Rheumatol 1986;5:382–8. 28. Gobelet C, Waldburger M, Meier JL. The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain 1992;48:171–5. 29. Gracely RH, Lynch SA, Bennett GJ. Painful neuropathy: Altered central processing maintained dynamically by peripheral input. Pain 1992;51:175–94. 30. Hall GC, Carroll D, Parry D, et al. Epidemiology and treatment of neuropathic pain: The UK primary care perspective. Pain 2006;122:156–62. 31. Heerschap A, den Hollander JA, Reynen H, et al. Metabolic changes in reflex sympathetic dystrophy: A 31P NMR spectroscopy study. Muscle Nerve 1993;16:367–73. 32. Hill A. Phantom limb pain: A review of the literature on attributes and potential mechanisms. J Pain Symptom Manage 1999;17:125–42. 33. Holder LE, Cole LA, Myerson MS. Reflex sympathetic dystrophy in the foot: Clinical and scintigraphic criteria. Radiology 1992;184:531–5. 34. Ibuki T, Hama AT, Wang XT, et al. Loss of GABA-immunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts. Neuroscience 1997;76:845–58. 35. Jaeger H, Maier C. Calcitonin in phantom limb pain: A double-blind study. Pain 1992;48:21–7. 36. Jensen TS, Krebs B, Nielsen J, et al. Immediate and long-term phantom limb pain in amputees: Incidence, clinical characteristics and relationship to pre-amputation limb pain. Pain 1985;21:267–78. 37. Kajander KC, Bennett GJ. Onset of a painful peripheral neuropathy in rat: A partial and differential deafferentation and spontaneous discharge in A beta and A delta primary afferent neurons. J Neurophysiol 1992;68:734–44. 38. Kaki AM, El Yaski AZ, Youseif E. Identifying neuropathic pain among patients with chronic low-back pain: Use of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. Reg Anesth Pain Med 2005;30:422–8. 39. Katz J, Melzack R. Pain “memories” in phantom limbs: Review and clinical observations. Pain 1990;43:319–36. 40. Katz N. Neuropathic pain in cancer and AIDS. Clin J Pain 2000;16:S41–S48. 41. Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain 1997;73:123–39. 42. Koltzenburg M, Scadding J. Neuropathic pain. Curr Opin Neurol 2001;14:641–7.

250 Kwok Fu Jacobus NG

43. Komori K, Nonaka T, Okada A, et al. Absence of mechanical allodynia and A beta-fiber sprouting after sciatic nerve injury in mice lacking membrane-type 5 matrix metalloproteinase. FEBS Lett 2004;557:125–8. 44. Kroner K, Krebs B, Skov J, et al. Immediate and long-term phantom breast syndrome after mastectomy: Incidence, clinical characteristics and relationship to pre-mastectomy breast pain. Pain 1989;36:327–34. 45. Leijon G, Boivie J. Central post-stroke pain — a controlled trial of amitriptyline and carbamazepine. Pain 1989;36:27– 36. 46. Mackenzie N. Phantom limb pain during spinal anaesthesia. Recurrence in amputees. Anaesthesia 1983;38:886–7. 47. Madison DV, Malenka RC, Nicoll RA. Mechanisms underlying long-term potentiation of synaptic transmission. Annu Rev Neurosci 1991;14:379–97. 48. Manicourt DH, Brasseur JP, Boutsen Y, et al. Role of alendronate in therapy for post-traumatic complex regional pain syndrome type I of the lower extremity. Arthritis Rheum 2004;50:3690–7. 49. Mao J, Chen LL. Systemic lidocaine for neuropathic pain relief. Pain 2000;87:7–17. 50. Max MB, Schafer SC, Culnane M, et al. Association of pain relief with drug side effects in postherpetic neuralgia: A single-dose study of clonidine, codeine, ibuprofen, and placebo. Clin Pharmacol Ther 1988;43:363–71. 51. Melzack R, Wall PD. Pain mechanisms: A new theory. Science 1965;150:971–9. 52. Merskey H, Bogduk N. Classification of Chronic Pain, 2nd edn. Seattle: IASP Press, 1994. 53. Moalem G, Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain. Brain Res Brain Res Rev 2006;51:240–64. 54. Moore KA, Kohno T, Karchewski LA, et al. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci 2002;22:6724–31. 55. Ness TJ, San Pedro EC, Richards JS, et al. A case of spinal cord injury-related pain with baseline rCBF brain SPECT imaging and beneficial response to gabapentin. Pain 1998;78:139–43. 56. Nordin M, Nystrom B, Wallin U, et al. Ectopic sensory discharges and paresthesiae in patients with disorders of peripheral nerves, dorsal roots and dorsal columns. Pain 1984;20:231–45. 57. O’Brien SJ, Ngeow J, Gibney MA, et al. Reflex sympathetic dystrophy of the knee. Causes, diagnosis, and treatment. Am J Sports Med 1995;23:655–9. 58. Ochoa J, Torebjork E. Sensations evoked by intraneural microstimulation of C nociceptor fibres in human skin nerves. J Physiol 1989;415:583–99. 59. Ochoa JL. Pain mechanisms in neuropathy. Curr Opin Neurol 1994;7:407–14. 60. Ochoa JL, Torebjork HE. Paraesthesiae from ectopic impulse generation in human sensory nerves. Brain 1980;103:835– 53. 61. Omer G, Thomas S. Treatment of causalgia. Review of cases at Brooke General Hospital. Tex Med 1971;67:93–6. 62. Panerai AE, Monza G, Movilia P, et al. A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain. Acta Neurol Scand 1990;82:34–8. 63. Perez RS, Zuurmond WW, Bezemer PD, et al. The treatment of complex regional pain syndrome type I with free radical scavengers: A randomized controlled study. Pain 2003;102:297–307. 64. Pochaczevsky R. Thermography in post-traumatic pain. Am J Sports Med 1987;15:243–50. 65. Roberts WJ. A hypothesis on the physiological basis for causalgia and related pains. Pain 1986;24:297–311. 66. Rosenberg JM, Harrell C, Ristic H, et al. The effect of gabapentin on neuropathic pain. Clin J Pain 1997;13:251–5. 67. Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of postherpetic neuralgia: A randomized controlled trial. JAMA 1998;280:1837–42. 68. Rowbotham MC, Davies PS, Fields HL. Topical lidocaine gel relieves postherpetic neuralgia. Ann Neurol 1995;37:246– 53. 69. Rowbotham MC, Davies PS, Verkempinck C, et al. Lidocaine patch: Double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain 1996;65:39–44. 70. Rowbotham MC, Reisner-Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology 1991;41:1024–8. 71. Sabatowski R, Galvez R, Cherry DA, et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: Results of a randomised, placebo-controlled clinical trial. Pain 2004;109:26–35. 72. Samad TA, Moore KA, Sapirstein A, et al. Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 2001;410:471–5. 73. Sato J, Perl ER. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury. Science 1991;251:1608–10. 74. Simone DA, Sorkin LS, Oh U, et al. Neurogenic hyperalgesia: Central neural correlates in responses of spinothalamic tract neurons. J Neurophysiol 1991;66:228–46. 75. Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: An update and effect related to mechanism of drug action. Pain 1999;83:389–400. 76. Sommer C. Painful neuropathies. Curr Opin Neurol 2003;16:623–8.

Neuropathic Pain 251

77. Stanton-Hicks M, Janig W, Hassenbusch S, et al. Reflex sympathetic dystrophy: Changing concepts and taxonomy. Pain 1995;63:127–33. 78. Stanton-Hicks M, Salamon J. Stimulation of the central and peripheral nervous system for the control of pain. J Clin Neurophysiol 1997;14:46–62. 79. Taha JM, Tew JM Jr. Comparison of surgical treatments for trigeminal neuralgia: Re-evaluation of radiofrequency rhizotomy. Neurosurgery 1996;38:865–71. 80. Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for complex regional pain syndrome: A systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors. Eur J Pain 2006;10:91–101. 81. Tesfaye S, Watt J, Benbow SJ, et al. Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy. Lancet 1996;348:1698–701. 82. Torrance N, Smith BH, Bennett MI, et al. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain 2006;7:281–9. 83. Varenna M, Zucchi F, Ghiringhelli D, et al. Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. J Rheumatol 2000;27:1477–83. 84. Veldman PH, Reynen HM, Arntz IE, et al. Signs and symptoms of reflex sympathetic dystrophy: Prospective study of 829 patients. Lancet 1993;342:1012–6. 85. Vestergaard K, Andersen G, Gottrup H, et al. Lamotrigine for central post-stroke pain: A randomized controlled trial. Neurology 2001;56:184–90. 86. Wall PD, Devor M. Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats. Pain 1983;17:321–39. 87. Wall PD, Gutnick M. Ongoing activity in peripheral nerves: The physiology and pharmacology of impulses originating from a neuroma. Exp Neurol 1974;43:580–93. 88. Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: A randomized trial in postherpetic neuralgia. Neurology 1998;50:1837–41. 89. Watson CP, Tyler KL, Bickers DR, et al. A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. Clin Ther 1993;15:510–26. 90. Watson PN, Evans RJ. Postherpetic neuralgia. A review. Arch Neurol 1986;43:836–40. 91. Woolf CJ. The pathophysiology of peripheral neuropathic pain — abnormal peripheral input and abnormal central processing. Acta Neurochir Suppl (Wien) 1993;58:125–30. 92. Woolf CJ, Doubell TP. The pathophysiology of chronic pain — increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol 1994;4:525–34. 93. Woolf CJ, Thompson SW. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation: Implications for the treatment of post-injury pain hypersensitivity states. Pain 1991;44:293– 9. 94. Xu XJ, Maggi CA, Wiesenfeld-Hallin Z. On the role of NK-2 tachykinin receptors in the mediation of spinal reflex excitability in the rat. Neuroscience 1991;44:483–90. 95. Zuurmond WW, Langendijk PN, Bezemer PD, et al. Treatment of acute reflex sympathetic dystrophy with DMSO 50% in a fatty cream. Acta Anaesthesiol Scand 1996;40:364–7.

16

Chak Sing LAU

Painful Arthritis and Rheumatic Conditions

Epidemiology and Impact of Arthritis and Rheumatic Diseases EPIDEMIOLOGY AND IMPACT OF ARTHRITIS AND RHEUMATIC DISEASES CLASSIFICATION OF ARTHRITIS AND RHEUMATIC DISEASES AN OVERVIEW OF THE TREATMENT OF ARTHRITIS AND RHEUMATIC DISEASES NON-STEROIDAL ANTIINFLAMAMTORY DRUGS AND SELECTIVE CYCLO-OXYGENASE-2 INHIBITORS COMMON ARTHRITIS CONDITIONS Osteoarthritis Rheumatoid arthritis Ankylosing spondylitis and related conditions Gouty arthritis Periarticular and regional rheumatic pain syndromes CONCLUSION REFERENCES

The increased life expectancy recorded in recent decades, together with changes in lifestyle and diet, has led to a rise in the incidence of non-communicable diseases globally. Of the various non-communicable diseases, rheumatic or musculoskeletal disorders are the major cause of morbidity throughout the world, having a substantial influence on health and quality of life, and inflicting an enormous burden of cost on health systems. In 1998, an estimated 355 million people suffered from arthritis [91]. This number is expected to rise dramatically over the next two decades so that by 2025 degenerative bone and joint disorders will be the commonest cause of physical disabilities accounting for one-quarter of all incapacitating conditions [82]. As a result of the epidemic of musculoskeletal disease that is occurring worldwide, the Bone and Joint Decade (BJD) was launched in Geneva by the World Health Organization (WHO) in 2000 [12]. The Decade has four major aims: 1. to raise awareness of the growing burden of musculoskeletal disorders on society; 2. to promote prevention of musculoskeletal disorders and empower patients through education campaigns; 3. to advance research on prevention, diagnosis and treatment of musculoskeletal disorders; and 4. to improve diagnosis and treatment of musculoskeletal disorders. In a major report on the burden of musculoskeletal diseases published by the WHO in collaboration with the BJD (WHO 2003), rheumatoid arthritis (RA) and osteoarthritis (OA), osteoporosis, spinal disorders, low back pain, and severe trauma have been identified as frequent causes of disability severely affecting individuals’ ability to carry out

254 Chak Sing LAU

Table 16.01

Estimated burden of musculoskeletal diseases by gender and developed or developing regions, 2001 [12]

Percentage of total DALYS RA OA Other MS diseases All MS diseases

Total 0.32 1.12 0.59 2.03

Male 0.18 0.86 0.65 1.69

Female 0.49 1.39 0.52 2.40

Developing regions (both genders) 0.27 0.91 0.56 1.74

Developed regions (both genders) 0.59 2.05 0.73 3.37

DALYS = disability-adjusted-life-years; MS = musculoskeletal; OA = osteoarthritis; RA = rheumatoid arthritis. (Table adopted with the permission of Dr. Peter M. Brooks.)

their activities of daily living and that this burden is seen in both the developed and developing countries (Table 16.01). Within a decade of onset, RA leads to work disability, defined as a total cessation of employment, in 51–59% of patients. In cases with OA, 80% of patients have some degree of limitation of movement and 25% cannot perform their major daily activities of life. Osteoporosis is another major cause of morbidity and mortality as osteoporotic fractures always require hospitalisation, are fatal in 20% of cases and permanently disable a further 50% of patients. In 1990, a worldwide estimate of 1.7 million hip fractures occurred as a result of osteoporosis, of which only 30% recovered fully. The number of hip osteoporotic fractures is expected to rise to 6 million by 2050. Low back pain has reached epidemic proportions, being reported by about 80% of people at some time in their life. The cost of arthritis and rheumatism conditions also appears to be growing with the ageing of the population, increased utilisation of new medical technologies and loss of work. In the United States, for example, this is now approaching 3% of the gross domestic product (GDP), which is equivalent to a permanent severe economic recession. The economic impact of RA is in the range of US$4,000–6,000 per case for direct cost and US$12,000–24,000 for indirect cost [92]. While the impact of arthritis and rheumatic diseases on the economy is high, the prevalence of these conditions does not accurately reflect the proportion of the population who may be suffering physically and/or psychologically. One of the areas

that is often not emphasised in musculoskeletal epidemiology studies is that of musculoskeletal pain. In a study based on two population-based cross-sectional surveys conducted over 40 years apart, a high prevalence of musculoskeletal pain, particularly in the shoulder and back, was observed in a community in the United Kingdom and also that there was a two- to four-fold increase over the 40-year period [29]. The observation of a high prevalence of musculoskeletal pain is mirrored in other populations around the world, including both industrialised and developing countries [14, 18, 30, 51, 63]. In many of these studies, not only is musculoskeletal pain found to be associated with significant physical and psychological suffering, but it is a major cause of work day and productivity loss. In the management of arthritis and rheumatic diseases, therefore, treatment should target correction of the underlying pathology, as well as pain control.

Classification of Arthritis and Rheumatic Diseases Arthritis and rheumatic diseases include more than 150 different conditions and syndromes with the common denomination of pain and inflammation. There have been many attempts to classify these conditions. However, most have been hampered by the lack of a firm pathoaetiological basis for many of these syndromes. Thus, working classifications used in individual practices, disease discussions and investigations are often dynamic as our understanding of these conditions evolves.

Painful Arthritis and Rheumatic Conditions 255

Table 16.02

Classification of arthritis and rheumatic diseases

1. 2. 3. 4.

Systemic connective tissue diseases Vasculitides Arthritis associated with spondylitis Rheumatic diseases associated with infectious agents 5. Bone and cartilage diseases 6. Rheumatic diseases associated with metabolic, endocrine and haematological disorders 7. Periarticular and regional rheumatic pain syndromes 8. Rheumatic syndromes associated with systemic medical disorders including neoplasms and tumour-like lesions 9. Rheumatic syndromes associated with hereditary, congenital and inborn errors of metabolism 10. Miscellaneous rheumatic disorders

In 1983, the American College of Rheumatology (ACR, formerly American Rheumatism Association) classified arthritis and rheumatic conditions based on their pathoaetiology and clinical presentation [20]. While it is considered to be the most comprehensive outline of known arthritis and rheumatic diseases, many find this classification overwhelming and cumbersome. In general, most of the rheumatic diseases can be grouped under 10 major categories (Table 16.02). Systemic connective tissue diseases include RA, juvenile idiopathic arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, polymyositis, dermatomyositis, polymyalgia rheumatica, etc. These conditions are characterised by various immune aberrations and patients present with a wide variety of clinical manifestations including constitutional symptoms, arthritis and other major organ disease. Many patients with systemic connective tissue diseases develop vasculitic complications (secondary vasculitis) involving mainly the small blood vessels. However, a distinct group of patients present with features characterised by a primary vascular inflammatory and necrotising pathology. These patients are said to have a primary vasculitide. Examples of primary vasculitides include polyarteritis nodosa, Wegener’s granulomatosis, Churg Strauss syndrome, giant cell arteritis, Takayasu’s arteritis and Henoch Schonlein purpura. Almost all of these conditions are associated with significant morbidity and

mortality. Treatment usually involves the use of high dose glucocorticoids and immunosuppressive drugs. Arthritis associated with spondylitis is also often referred as sero-negative spondyloarthritis (SpA). This form of arthritis includes ankylosing spondylitis (AS), psoriatic arthritis, arthritis associated with inflammatory bowel diseases and Reiter’s syndrome. These conditions share several common features, including familial aggregation, asymmetric joint involvement and mucocutaneous lesions. Some of these conditions may follow gastrointestinal (GI) or sexually acquired infections and may be associated with human immunodeficiency virus (HIV). Reiter’s syndrome is one such classical condition and patients present with urethritis, conjunctivitis and arthritis (which is sterile) following infectious dysentery. The major causes of septic arthritis can be viral, bacterial, fungal, or helminthic. Each can present as either a polyarticular presentation or a monoarthritis. Many of the helminthic infections present with more generalised aches and pains and involvement of muscle tissues as well as joints. All the conditions have specific diagnostic features and treatments. Bacterial infection of the joint is a potential serious cause of morbidity, mortality, joint damage and functional disability and warrants immediate antibiotic treatment. As has been highlighted above, osteoporosis and OA are the most important bone and cartilage diseases respectively. Osteoporosis is characterised by low bone mass and deterioration in the microarchitecture of the bone, which leads to fracture after minor or moderate trauma. It is defined by diagnostic criteria based on bone mineral density as follows: a bone mineral density of more than -2.5 standard deviations below the average bone mineral density of young adult women. Clinical features of osteoporosis are primarily due to its major outcome: fracture which commonly occurs in the distal radius, vertebrae, or hip often following minor trauma. Vertebral fractures lead to loss of height, kyphosis and back pain. The incidence of fracture varies with country and with type of fracture. Hip fractures are low in African countries but high and increasingly reported in Australasia, Europe and North America. Fracture risk increases with age and is beginning to have a significant impact on quality of life, mortality and health care costs in many countries [69]. Other important causes of bone disease include rickets,

256 Chak Sing LAU

osteomalacia, hypertrophic osteoarthropathy, avascular osteonecrosis and Paget’s disease. Crystal arthritis, particularly gouty arthritis, is probably the commonest rheumatic disease associated with a metabolic disorder. Gout is characterised by tissue deposition of crystals of monosodium urate from supersaturated extracellular fluids and may result in acute or chronic arthritis and periarthritis, tophaceous deposition and gouty nephropathy. Its prevalence has increased over the last few decades in countries with a high standard of living. Regional rheumatic pain syndromes or soft tissue rheumatism (STR) are among the most commonly encountered rheumatic complaints and yet they are often overlooked. The diagnosis of most of these lesions relies on the physician’s clinical acumen, and a thorough understanding of the anatomy and function of the soft tissue involved is essential. Other rheumatic diseases are less commonly encountered but should not be overlooked. For example, it is not uncommon for patients with an underlying malignant condition to present with arthritis. It is beyond the scope of this chapter to describe all of the rheumatic diseases listed above. However, a brief account of the epidemiology, pathoaetiology, clinical presentation and management of common conditions including RA, AS and related conditions, OA, gouty arthritis and STR will be given below.

An Overview of the Treatment of Arthritis and Rheumatic Diseases The principles in the management of all forms of arthritis and rheumatic diseases are similar. A multidisciplinary approach involving the rheumatologist, orthopaedic surgeon, pain specialist, family physician, specialty nurse, physiotherapist, occupational therapist, social worker, podiatrist and clinical psychologist is commonly employed. The main objective is to reduce pain and enable the patient to maintain as near normal a life as possible. Effective communication between physician and patient is important. Educating the patient and his or her family about the cause, treatment and prognosis of the underlying condition, particularly chronic arthritis, is useful in allaying

anxiety and improving treatment compliance. Misunderstandings about the disease may lead to frustration, depression and withdrawal. In recent years, self-management education, with emphasis on theory-based self-management support, has also been shown to have significant positive effects on patient knowledge, behaviours and health outcomes. Furthermore, the importance of patient support groups must not be overlooked. People with arthritis often have limited range of motion, decreased muscle strength and endurance. Together with possible changes in gait and posture, chronic arthritis often leads to functional limitations and general deconditioning. Physiotherapists can recommend appropriate regular physical activity and exercises which can lead to improvements in these areas and can reduce pain, fatigue and depression. Besides, physical agents of heat, cold and electricity may be used to alleviate the symptoms of rheumatic diseases. Wax baths, ice packs, ultrasound and weak electrical current stimulation (interferential therapy) are useful treatment modalities for patients with chronic arthritis. Occupational therapists can advise on joint protection and can provide aids and appliances which allow chronic arthritis sufferers to be independent. Splints are extensively used to protect, immobilise, or mobilise various parts of the body. They are also used to prevent and correct deformities and are particularly useful in the management of hand arthritis in patients with RA. Surgery also has an important role in the management of many arthritis and rheumatic diseases. Useful operations range from the removal of local areas of diseased synovial tissue, to the removal of subluxed joints and total joint replacement in patients with chronic diseases such as RA and AS. It is beyond the scope of this chapter to discuss the many forms of surgical interventions available in the management of chronic arthritis. The use of drugs has a central role in the treatment of chronic arthritis. The ideal drug should provide symptomatic relief and eradicate the underlying condition without causing side effects. While such a drug(s) is not yet available and there is still no cure, progress made in recent years in our understanding of arthritis means that it is now possible to keep arthritis symptoms under good control with judicious use of therapeutic agents that are well tolerated and specific in their mechanisms

Painful Arthritis and Rheumatic Conditions 257

of action. Broadly, these agents may be divided into those that provide symptomatic relief, and others which are capable of delaying disease progression — the so called disease modifying anti-rheumatic drugs (DMARDs).

Non-Steroidal AntiInflammatory Drugs and Cyclo-Oxygenase-2 Selective Inhibitors Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed symptom relieving drugs for arthritis and rheumatic diseases. The primary mechanism of action of NSAIDs is due to their inhibitory effects on the production of pro-inflammatory prostaglandins via the enzyme cyclo-oxygenase (COX) [87]. Unfortunately, the use of NSAIDs is limited by their high incidence of adverse reactions, particularly upper GI tract erosion and ulceration, bleeding tendency and renal toxicity due to their inhibitory actions on GI mucosal, endothelial and renal prostaglandin synthesis, particularly PGE2 and PGI2. Nonsteroidal anti-inflammatory drug-induced upper GI complications are major iatrogenic disorders. The point prevalence of upper GI ulceration ranges from 10–20% [47]. Of clinical importance are ulcers that cause symptoms or develop into Table 16.03 Risk factors for serious upper gastrointestinal complications associated with NSAID use • Previous history of peptic ulcer disease, upper GI bleeding and GI hospitalisation • Prior NSAID-associated GI side effects • Old age • Arthritis-related disability • High dose or multiple NSAIDs being used • Concurrent high dose steroid use • History of cardiovascular disease • Concurrent use of H2 antagonists or antacids • The requirement of symptomatic treatment indicates an increased risk • Antacids and H2 antagonists (at ordinary doses) do not prevent NSAID-induced gastric ulcers but may mask relevant symptoms and delay medical attention

potentially life-threatening complications such as upper GI bleeding, perforation and gastric outlet obstruction. These complications are reported to occur in 2–4% of patients taking NSAIDs for 1 year [61]. Table 16.03 shows the risk factors for serious upper GI complications associated with NSAID use [74, 75]. Unfortunately, most chronic arthritis patients who require long-term NSAID therapy belong to one or more of these categories. It is now known that COX exists in 2 isoforms: COX-1 and COX-2 (Simmons et al., 1989). COX1 is the constitutive form of the enzyme which is present in many tissues including the gastric mucosa, endothelium, kidney and platelets. COX1 has clear physiological functions; it produces prostaglandins involved in cytoprotective and regulatory functions of these organs. Gastric prostaglandins are derived almost exclusively from COX-1. In contrast, the activity of COX2 is normally very low in cells except in those of the brain, reproductive organs and kidney. COX2 is tightly controlled by a number of factors including cytokines and intracellular messengers, and by the availability of substrate. Its expression is rapidly induced in the context of inflammation (and other pathological conditions) [58]. COX-2 is unregulated in inflammatory cells such as activated macrophages and synoviocytes in patients with chronic arthritis such as RA. All currently available NSAIDs inhibit COX-1 and COX-2, each to varying degrees. Thus, the anti-inflammatory effects of NSAIDs are mediated through COX-2 inhibition while their typical adverse effects in the GI tract and antiplatelet effects result mainly from the inhibition of COX-1. Selective COX-2 inhibitors have been approved for use in common arthritis conditions. These drugs were considered a revolution in pain management because of their ability to relieve pain and inflammation while being less toxic to the GI tract [9, 73]. However, this wave of enthusiasm has recently been blunted with studies which showed that selective COX-2 inhibition is associated with an increased risk of vascular thrombosis [9, 77]. Confusion followed when recent large population studies showed similar vascular risk increase with long-term NSAID use [27, 36, 76]. While the COX2 inhibitors/NSAID stories may have caused panic in patients and medical practitioners alike, they have been positive when viewed from a different angle. First, most of the findings, desirable or not,

258 Chak Sing LAU

were made in unprecedented large scale outcome studies. This not only emphasises that modern medicine is evidence based but sets a new standard for evaluating future therapies, which ultimately means enhanced safety for our patients. Second, the swift actions taken by the pharmaceutical firms and regulatory authorities involved should reassure patients and prescribers that patient safety is in the forefront of their considerations. Third, carers of patients with rheumatic disorders should learn from these lessons that treatment of pain syndromes involves not only the use of anti-inflammatory drugs but a multidisciplinary approach involving a number of other drug and non-drug modalities. The pros and cons of all pharmaceutical agents must be carefully weighed before they are used. Please also refer to Chapter 22 for more details on NSAIDs and COX-2 inhibitors.

Common Arthritis Conditions Osteoarthritis Scope of the problem OA is the most common form of arthritis, encompassing 60–70% of all joint diseases. It is commonly referred to as a degenerative arthritis and is a major health problem throughout the world, second among causes of permanent incapacity in people over age 50 years. Radiographic evidence of OA can be found at some site in the majority of people older than 65 years of age, while more than 80% of those over the age of 75 are affected. However, estimates of the incidence of OA are imprecise because of the difficulties in defining the condition and how to determine its onset. It is also important to note that less than one-half of all those with radiographically identifiable OA have symptoms. Worldwide estimates are that 9.6% of men and 18.0% of women aged 60 years or above have symptomatic OA [57]. However, racial differences exist for both the prevalence of OA and the pattern of joint involvement. In general, OA is more prevalent in Europe and the USA than in other parts of the world. For example, African-American women are more prone than white women to OA of the knee but not the hip — similarly in South African blacks, South Asian Indians and Chinese [81].

While the prevalence of OA increases with age, in any given joint, OA may result from a combination of risk factors including genetic predisposition, local aetiological factors, such as trauma, and comorbidities. For example, there is a strong genetic component in primary nodal OA which is often found in women of menopausal age and most commonly affects the proximal interphalangeal (Bouchard’s nodes) and distal interphalangeal (Heberden’s nodes) joints of the hand. Further, patients with primary nodal OA are more likely to develop secondary OA of the knee after menisectomy [21]. Local trauma may speed up the joint degeneration process. For example, people who are obese are more prone to develop OA as their joints are constantly under more stress. Severe and recurrent trauma to the joint may also predispose to the development of OA. Many athletes suffer from OA due to excessive use and recurrent trauma to their joints. Co-morbidities include other chronic arthritis such as RA and sero-negative SpA. This is because a diseased joint is more likely to be subject to an abnormal distribution of load and hence more liable to accelerated degeneration. Table 16.04 shows the risk factors for the incidence and progression of OA. Data are available from developed countries on the economic consequences of work loss from OA, health resource utilisation and joint replacements (most of which are carried out for OA). In Australia, the total health system cost for OA in 1993–1994 Table 16.04 Risk factors for the incidence and progression of osteoarthritis • • • • • • •

•

Hereditary Age Female sex Congenital deformities, e.g. slipped capital epiphyses in the hip Local trauma, previous injuries and physically demanding activities High bone mass index Co-morbidities • coexisting inflammatory arthritis, e.g. RA, AS • coexisting metabolic disorders, e.g. diabetes, gout, acromegaly, ochronosis • coexistent neurological disorders, e.g. Charcot arthropathy Smoking (protective)

Painful Arthritis and Rheumatic Conditions 259

was AUS$624 million, which accounted for 21% of the total expenditure on musculoskeletal diseases. There were approximately 41,000 hospital admissions, 13.9% of all hospitalisations for musculoskeletal conditions (n = 295,000). The average length of hospital stay for OA was 9.4 days, whereas that for all musculoskeletal conditions combined was 5.0 days. In the same year period (1993–1994), patients with OA also received the greatest number of prescriptions (3,058,400), accounting for 22.9% of all prescriptions written for musculoskeletal disease [55]. In other developed countries such as the USA, Canada, the UK and France, the total cost of OA has been estimated to vary from 1–2.5% of GNP [53].

Clinical presentation of osteoarthritis Almost all joints may be affected by OA. However, joints that bear the most weight are more liable to develop wear and tear. Osteoarthritis therefore commonly affects the hip, knee and lumbar spine. Joints that are mobile, e.g. the first carpometacarpal joint (base of the thumb), distal interphalangeal joints (end joints of the fingers) and the neck, may also develop OA. The wrists, shoulders and ankles are less often involved. Not all patients with joint symptoms have radiographic changes; and not all radiographic changes are associated with joint symptoms. Pain is the predominant complaint of all patients symptomatic of OA. This tends to be worse after exercise and towards the end of the day, and is relieved by rest. Patients usually feel at their best first thing in the morning. In addition to pain, there may be stiffness (gelling), which is worse after prolonged inactivity. The joint may feel swollen and bony. Although OA is essentially a degenerative disease of the joint, there may be a minor component of inflammation and some patients complain of an increase in temperature and redness of the joint. In some cases, OA may be complicated by deposition of calcium crystals within the joint and patients present with an acute onset of intense pain, swelling and redness of the affected joint. These symptoms mimic those of gout and the complication is called pseudo-gout. Blood tests are usually unhelpful, but they may sometimes reveal underlying metabolic disorders. Radiographs may show loss of joint space resulting from cartilage damage, osteophytosis (formation of

new bone), altered bone contour and subchondral sclerosis (increased bone density), and cystic formation resulting from bony remodelling. There may also be soft tissue swelling and periarticular calcification.

Management of osteoarthritis Guidelines for OA management have been developed by the ACR [3] and the European League Against Rheumatism (EULAR) [35, 93]. The treatments recommended in these guidelines should be tailored to each individual patient, carefully weighing adverse event risks relative to potential benefits. Patient education must be emphasised as misconceptions exist about this disease at both extremes. Many patients require only reassurance that they have no generalised crippling form of rheumatic diseases. The primary treatment objectives include pain relief and restoration of function. The general principles in the management of various forms of arthritis conditions have been highlighted above. A multidisciplinary approach is essential. Physical therapy includes protection of joints from overuse, particularly if weight-bearing joints are involved. Weight reduction should be advised, especially in patients with marked obesity. Appropriate exercises should be taught to strengthen the various muscle groups acting on the affected joint. Pharmacological therapies are primarily used to alleviate painful symptoms. Analgesic agents such as paracetamol (acetaminophen), administered on a regular basis, are frequently effective. Other analgesic agents such as propoxyphene hydrochloride may be used temporarily as needed. Opioid preparation, required only occasionally for acute flares, should be very limited in use. The use of NSAIDs has been described in more detail above. It should be noted that oral or parenteral use of glucocorticoids is generally not indicated in the treatment of OA, although intra-articular injection of these agents may be beneficial when used judiciously in the management of acute disease flares. However, injections should be infrequent, especially if given in weight-bearing joints. Joint deterioration may be accelerated due to masking of pain and subsequent joint overuse or to a direct deleterious effect of these drugs on cartilage. Pericapsular and ligamentous injections in areas of

260 Chak Sing LAU

tenderness around involved joints can provide relief with less hazard [32, 46]. Besides glucocorticoids, synthetic and naturally occurring hyaluronan derivatives have also been delivered intra-articularly in the management of mild to moderate OA of the knee [33]. These compounds have so far been shown to be effective in alleviating joint symptoms. However, several injections are required and some patients may experience a flare of symptoms after injection. Furthermore, additional studies are needed to evaluate the long-term effects of these agents [62]. The search for a disease modifying anti-OA drug has remained an intense pursuit of many clinicians and OA sufferers. Many patients with OA use numerous nutriceuticals including glucosamine and chondroitin sulphate. Both have been reported in in-vitro studies to stimulate proteoglycan synthesis and inhibit degradative enzymes. Although quite different in molecular weight, both appear to be significantly absorbed after oral administration, with a low toxicity profile and delayed onset of action. Unfortunately, despite multiple controlled clinical trials of the use of these agents, particularly glucosamine sulphate, in OA (mainly of the knee), controversies on efficacy related to symptomatic improvement continue. Differences in results originate from the differences in products, study design and study populations. A recent metaanalysis study shows there is evidence to support the continued consideration of glucosamine sulphate in the OA therapeutic armamentarium and that this agent may reduce the progression of knee OA [66]. It should, however, be remembered that the manufacture of nutriceutical/dietary supplements is not regulated; therefore the various products available are not standardised and results obtained with glucosamine sulphate from controlled clinical trials may not be extrapolated to other salts (hydrochloride) or formulations (overthe-counter or food supplements) for which no warranty exists about content, pharmacokinetics and pharmacodynamics in the labels.

Rheumatoid arthritis Epidemiology and pathoaetiology of rheumatoid arthritis Rheumatoid arthritis is the commonest form of chronic inflammatory arthritis. The definition of RA used in epidemiological studies has changed

Table 16.05 The 1987 American College of Rheumatology revised classification criteria for rheumatoid arthritis [4] Criterion

Definition

1

Morning stiffness

Morning stiffness in or around the joint, lasting at least 1 hour before maximal improvement

2

Arthritis of 3 or more joint areas

At least 3 joint areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed by a physician. The 14 possible areas are the right or left PIP, MCP, wrist, elbow, knee, ankle and MTP joints

3

Arthritis of hand joints

At least 1 area swollen (as defined above) in a wrist, MCP or PIP

4

Symmetric arthritis

Simultaneous involvement of the same joint areas (as defined above) on both sides of the body (bilateral involvement of the PIPs, MCPs or MTPs is acceptable without absolute symmetry)

5

Rheumatoid nodules

Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxta-articular regions, observed by a physician

6

Serum rheumatoid factor

Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in 70%) present with a bilateral and symmetrical polyarthritis, usually of insidious onset. All synovial joints may be affected, but peripheral joints are more commonly affected. These include the hand metacarpophalangeal and proximal interphalangeal joints, wrists, elbows, foot metatarsophalangeal and interphalangeal joints, ankles, knees and the temporomandibular joints. Involvement of the shoulder, hip, sternoclavicular and cricoarytenoid joints is less common. The axial skeleton, with the exception of the cervical spine, is usually spared. Patients complain of joint pain, stiffness and swelling which are worse in the early morning. Oedema and proliferation of the synovium contribute to stiffness by mechanically interfering with joint motion. The clinical course is that of relapse and remission [41]. Although RA is manifested primarily by joint involvement, it is a systemic inflammatory disease. Most patients experience constitutional symptoms with fatigue, malaise, anorexia, low grade fever and depression. These symptoms may precede overt arthritis by weeks or months. Some patients may also present with extra-articular features which are associated with a poorer overall prognosis. For example, subcutaneous nodules are found over bony prominences that are subject to external pressure, e.g. extensor surface of the elbow. Vasculitic skin rashes and nail fold and finger pulp infarcts are not uncommon. Keratoconjunctivitis sicca (dry eyes) and episcleritis are common ocular manifestations. Scleritis and scleromalacia are rare but serious, as they can lead to eyeball perforation. Other extraarticular manifestations may include serositis, fibrosing alveolitis, mononeuritis and renal amyloidosis [41]. There appears to be an ethnic variation in the manifestation of extra-articular disease. For example, these complications are less commonly reported in RA patients of Chinese origin [15]. The diagnosis of RA is based primarily on the patient’s clinical manifestations. However, laboratory investigations may reveal the presence of

262 Chak Sing LAU

rheumatoid factor, which is an antibody (typically IgM but may also be IgG or others) that binds to the Fc fragment of IgG, in approximately 70% of patients. It should be noted that rheumatoid factor is not wholly specific for RA as it may also be found in patients with non-RA disease such as systemic lupus erythematosus, Sjögren’s syndrome, hepatitis B and C infections, and malignancies [39]. Antibodies to cyclic citrullinated peptide (anti-CCP) have recently been identified as a more specific marker for RA with over 95% specificity. These antibodies, which can be detected several years before the development of clinical RA and that of rheumatoid factor, can be helpful in diagnosing RA in patients with rheumatoid factor-negative arthritis. Furthermore, they appear to be associated with more severe outcomes, with radiographic joint damage and an overall poorer prognosis [86]. Other common but less specific laboratory abnormalities include a normochromic, normocytic anaemia, mild leucocytosis and thrombocytosis, and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Radiographic findings vary depending on the duration and severity of the illness. A normal radiograph does not exclude a diagnosis of RA, although over half of patients develop radiographic changes within 2 years of disease onset. Classically, there is periarticular osteopenia, joint space narrowing and juxta-articular erosions. While plain radiographs are easily accessible, ultrasonography and magnetic resonance imaging (MRI) are more sensitive in detecting early disease.

Management of rheumatoid arthritis Recent evidence suggests that joint destruction in RA begins within a few weeks of symptom onset and that early treatment with effective pharmaceutical agents decreases the rate of disease progression [23, 80]. Patients with suspected RA should therefore be referred to a rheumatologist within 3 months of presentation for confirmation of diagnosis, as well as initiation of DMARDs. The goals of treatment of RA include relief of pain and inflammation, joint protection, preservation of function and quality of life, and control of systemic complications. Many agents have been shown to have disease modifying effects on RA. They include methotrexate, sulphasalazine, hydroxychloroquine, gold salts, penicillamine, azathioprine and cyclosporin A.

These so called DMARDs should be considered for all patients with RA [8]. Compliance, disease severity, physician experience and the presence of various comorbidities guide medication choice. The DMARDs share many common characteristics. They do not provide relief for RA symptoms and are slow in their onset of action. Besides, they have a relatively short “life span”. Most patients who are treated with a single DMARD come off their treatment after 3 to 5 years, due either to the loss of efficacy or development of side effects. Recently, however, it has been possible to better control RA by combining DMARDs [64]. For example, combination therapy with methotrexate, sulphasalazine and hydroxychloroquine has been shown to be more effective than sulphasalazine and hydroxychloroquine or methotrexate alone. It has also been shown that patients with early RA treated with methotrexate, sulphasalazine and hydroxychloroquine had a better chance of remission at 2 years than those treated with sulphasalazine alone. Results from other trials have also demonstrated that aggressive initial therapy with combinations of drugs could benefit patients without significantly increased toxicity. Newer DMARDs include leflunomide, which inhibits pyrimidine synthesis through its inhibitory effects on the dihydro-orotate dehydrogenase enzyme. Leflunomide is probably quicker in its speed of onset of action when compared with conventional DMARDs. It has been shown to reduce radiographic progression with efficacy similar to methotrexate and sulphasalazine in large clinical studies. Leflunomide may also be combined with methotrexate and sulphasalazine for patients with advanced disease without an increase in the frequency of adverse reactions [16]. It is not within the scope of this chapter to discuss the side-effect profiles of DMARDs. However, it is suffice to say that these drugs, including leflunomide, are potentially toxic and their use should be justified and closely monitored. Glucocorticoids also play an important role in the treatment of RA. When administered with care, intra-articular glucocorticoid injections can bring about remarkable relief to patients’ articular disease, particularly in patients with a monoarticular flare.

Painful Arthritis and Rheumatic Conditions 263

In addition, during the process, aspiration of the distended joint and concomitant administration of local anaesthetics can lead to an immediate relief. Intra-articular glucocorticoid injection may help to facilitate physical therapy and avoid the need to augment systemic treatment. However, care should be exercised to avoid the abuse of these injections. For example, it will be unwise to repeatedly inject the same joint many times when actually the more appropriate action should be a change in the systemic therapy or surgery. This is also true for a polyarticular flare of RA, when the systemic treatment should be adjusted instead of multiple joint injections. Systemic glucocorticoids may also be used as “bridging therapy” during the period when DMARDs have been initiated but have not yet taken effect. Chronic administration of glucocorticoid at dosages equivalent to less than 10 mg of prednisolone per day are highly effective for relieving symptoms of RA and can slow joint damage [38, 85]. However, glucocorticoid dosages should be kept at a minimum because of high risk of side effects, which include osteoporosis, cataract, hypertension, Cushingoid symptoms and glucose intolerance.

Biological agents for rheumatoid arthritis The outlook of patients with RA has been markedly improved in the past few years since the availability of biological therapies, thanks to a rapid development in the field of immunology and a better understanding of the immunopathology of this condition. Tumour necrosis factor (TNF)-alpha is known to play a central role in the pathogenesis of RA. This pro-inflammatory cytokine triggers several important events that lead to the synovitis and tissue destruction seen in RA. Besides, activation of the adhesion molecules promotes recruitment of inflammatory cells into the joint and causes further damage. Therapeutic intervention is now possible using agents that antagonise the effects of TNFalpha. Etanercept, infliximab and adalimumab are currently approved for the treatment of active RA. Etanercept is a soluble TNF-receptor fusion protein [8], while infliximab and adalimumab are a chimeric and human IgG1 anti-TNF-alpha antibody, respectively [48, 89]. All three agents have been demonstrated to have superior efficacy when compared with conventional DMARDs. Initial studies have focused on the use of these

drugs in patients with refractory disease who have failed conventional therapies including combination treatment. Not only do these drugs improve patients’ signs and symptoms of RA, improvements which become apparent within the first 2 weeks of treatment, their use is associated with delayed radiographic changes. Indeed, recent studies have also shown that these drugs are capable of reversing bony erosive lesions as demonstrated by MRI, suggesting that they may be true disease remitting agents of RA [56]. While anti-TNF-alpha agents are promising, their use is limited by their prohibitive cost. Few patients are able to afford these agents long term. Further, potential adverse reactions associated with their long-term use have not been fully documented yet. Of particular concern is the possible increase in susceptibility to various infections. Tuberculosis and hepatitis are major worries [56, 60]. Besides, whether the use of these agents may be associated with an increased risk of malignancies is not fully known, although post-marketing surveys have failed to substantiate this concern thus far. In addition to TNF-alpha, evidence has emerged supporting the pivotal role of B cells in the pathogenesis of RA. Rituximab, a chimeric monoclonal antibody to a specific marker for mature B cells (CD20) has recently been approved for treatment of RA refractory to anti-TNF-alpha therapy [22, 31]. Randomised pilot studies have shown B-cell depletion is an effective and safe approach to RA management. The B cell depletion with rituximab is rapid and may be prolonged for periods of >1 year. In general, patients tolerate this agent well with safety comparable to that of methotrexate, except for increased infections [31]. Infusion-related reactions are the most common adverse reactions. These may sometimes be severe and may be decreased with intravenous glucocorticoid pre-treatment at the time of the infusion. Other targets for biological therapies include IL1 [59], IL-6, adhesion molecules, T-cell activation molecules and T-B cell interaction molecules [26]. Many of these therapeutic agents have reached phase II or III stages of their development for human clinical use. Results have so far been encouraging. This is likely to further improve the prognosis and quality of life of patients with RA in future.

264 Chak Sing LAU

Ankylosing spondylitis and related conditions Epidemiology and pathoaetiology of ankylosing spondylitis and other spondyloarthritis Ankylosing spondylitis is the prototype of a group of conditions commonly known as the seronegative SpA and characterised by inflammation of the spine, peripheral joints and periarticular structures. These conditions are also variably associated with characteristic extra-articular manifestations such as anterior uveitis, mucocutaneous lesions, pulmonary fibrosis, aortic root lesions and cardiac conduction abnormalities. In addition to AS, other SpA include Reiter’s syndrome, reactive arthritis, SpA associated with psoriasis and inflammatory bowel disease, and a variety of less clearly defined conditions known as undifferentiated SpA. The underlying pathogenic mechanisms of SpA are not fully understood but it is almost certain that genetic factors are involved as most, though not all, of these disorders show an increased prevalence among individuals who have inherited the human leucocyte antigen (HLA)-B27 gene. The frequent demonstration of infection by microbes such as Chlamydia, Yersinia, Salmonella and Klebsiella in these genetically predisposed hosts suggests that interactions between genetic and environmental factors are pivotal in the pathogenesis of SpA [42]. Historically, AS was thought to be a disease that almost exclusively affected young men. However, cases in females are being increasingly recognised and the male to female ratio is now believed to be about 2 or 3 to 1 with considerable geographical and ethnic variations [42]. In general, female patients tend to have milder disease. Disease onset commonly occurs in late adolescence or early adulthood. The prevalence of AS has been reported to be extremely rare in Afro-Americans, 0.26– 0.38% in Chinese, 0.1–1.4% in Caucasian whites and up to 10% of all adult males in circumpolar Arctic and sub-Arctic populations [10, 42, 70]. Such variations appear to be related to the frequency of the HLA-B27 gene found in the corresponding populations, highlighting the importance of this gene in the development of AS. Several mechanisms for the pathogenic role of HLA-B27 in AS and other SpAs have been proposed. The fact that reactive arthritis and AS

are triggered by genitourinary intestinal infective agents that share sequence homology with HLAB27 has led to the theory of molecular mimicry with T-cell responses that have been elicited by the microbial agents’ cross-reaction with a host protein. An alternative proposed mechanism involves the primary function of HLA-B27 being antigen presentation. It is possible that the microbial agents are presented by HLA-B27 to CD8 T-cells and initiate an inflammatory response. Persistence of the microbial infection leads to perpetuation of this response and subsequent joint damage. Finally, it is possible that HLA-B27 itself may directly cause AS and other SpA as HLA-B27 transgenic rats develop SpA-like features, although many transgenic copies are needed to transfer disease [52].

Clinical manifestations of ankylosing spondylitis and other spondyloarthritis Inflammatory low back pain as a result of sacroiliac joint involvement is the commonest initial clinical manifestation of AS. There is associated morning stiffness and the pain is worse at rest and often felt in the buttocks, especially when seated. It may radiate to the back of the thighs mimicking sciatica, although the latter is usually unilateral and relieved by rest. As the disease progresses upwards, pain is experienced at higher spinal levels. Thoracic spine involvement may present with pleuritic chest pain, but unlike true pleurisy it is usually bilateral. On examination, there is loss of lumbar lordosis and a fixed kyphosis usually compensated for by extension of the cervical spine, eventually producing the stooped “question mark” posture. Sacroiliac joints are tender on percussion and springing of the pelvis. Movements of the spine at various levels are restricted and so is chest expansion. Changes in the peripheral joints, usually the larger ones, are similar to those seen in RA and show signs of inflammation. Extra-articular manifestations include iritis which may affect approximately 30% of patients and may sometimes precede spinal involvement. About 4% of patients develop aortitis with signs of aortic incompetence. Cardiac conduction defects and pulmonary restriction may also be apparent but are uncommon. Blood tests are often not very helpful. The ESR may be raised but RF is not present in the blood. HLA-B27 tissue typing is not of diagnostic value as although over 90% of patients possess this gene, approximately 6–8% of the population

Painful Arthritis and Rheumatic Conditions 265

(Caucasians) are HLA-B27 positive. However, a negative test for HLA-B27 often suggests the patient’s back symptoms are due to other underlying pathology. Radiological changes of sacro-iliitis include widening of joint space and juxta-articular erosions and sclerosis. In the spine, there is squaring of the vertebral bodies caused by erosion of their corners. Syndesmophytes (bony depositions) form at the margin of the vertebrae. These may join together and produce the classical appearance of a “bamboo spine”. There may also be radiological evidence of enthesopathy (calcification and new bone formation in the soft tissues) with erosions, sclerosis and soft-tissue calcification around the ischial tuberosities, iliac crests, greater trochanters, patellae and calcanea. Newer techniques such as computed tomography (CT) and MRI demonstrate considerably higher sensitivity in identifying sacroiliitis in the early stages of AS. Use of CT appears to be superior to MRI for the visualisation of chronic changes. On the other hand, MRI is the only technique that can image acute and chronic lesions simultaneously [6, 25]. The clinical manifestations of other reactive arthritis are similar to those of AS except that spinal disease may not always be apparent at first presentation. In Reiter’s syndrome, patients present with a classical symptom triad that comprises urethritis, conjunctivitis and arthritis. Extraarticular complications are common and involve the skin (keratoderma blenorrhagicum) and mucocutaneous surfaces — mouth ulcers, circinata balanitis and cervicitis.

Management of ankylosing spondylitis and spondyloarthritis For years, the standard treatment of spinal symptoms for patients with AS and related conditions has consisted of physiotherapy with structured exercise programmes and the use of NSAIDs. While a recent Cochrane review showed that there is little evidence for effectiveness of non-pharmacological intervention [17], there is a strongly positive expert opinion. The importance of a life-long programme of regular individual and group exercises, patient associations and self-help groups is particularly emphasised in the management of AS and other SpA. Swimming and hydrotherapy are very helpful. Warm water helps promote relaxation and reduces the discomfort of stretching. Furthermore, water exercises strengthen muscles because of the water’s

resistance, and increase cardiovascular conditioning and endurance. However, patients with psoriatic skin lesions should avoid chlorinated water. Deepbreathing exercises are also encouraged and can be prepared for by applying local heat or taking analgesics to relieve pain from costochondritis. Patients should be advised to avoid smoking. Non-steroidal anti-inflammatory drugs are the cornerstone of treatment in patients with AS. A good response to these drugs has been identified as a diagnostic sign for AS and other SpA, although a state of non-responsiveness to NSAIDs might suggest a poor prognosis [68]. To achieve the desired therapeutic effects, NSAIDs need to be taken regularly in full anti-inflammatory doses rather than the usual on-demand prescription. Previous studies have shown this to reduce radiographic progression [88]. The use of traditional DMARDs, including methotrexate, leflunomide and sulphasalazine, which are effective in RA, are not recommended for the treatment of AS axial disease. Sulphasalazine may be considered for patients with peripheral arthritis [13]. Bisphosphonates have recently been suggested to be useful for spinal symptoms of AS [50], but other studies have not been able to reproduce similar results [28]. The use of antibiotics is not supported by evidence from the literature except for cases of reactive arthritis preceded by a known bacterial infection, especially Chlamidya trachomatis [44]. Appropriate antibiotics may reduce the duration of reactive arthritis, but this therapy does not seem to alter the natural course of the disease. Blockade of the effects of TNF-alpha has markedly changed the treatment paradigm of AS and related conditions, and their outlook. TNF-alpha antagonists are remarkably effective in the treatment of AS patients with persistently high disease activity despite conventional therapy. In patients with axial disease, unlike with RA, there is no need for the use of DMARDs prior to or concomitant with anti-TNFalpha therapy. All three TNF-alpha antagonists, etanercept, infliximab and adalimumab, have been approved for AS [11, 19, 84]. These drugs are also dramatically effective in treating psoriasis, psoriatic arthritis and inflammatory bowel disease (except with etanercept). Thalidomide, which has some anti-TNF-alpha properties but is cheaper, has recently been suggested to be effective in AS in

266 Chak Sing LAU

an open-labelled study [34], but controlled trials are needed to prove its efficacy and safety in these patients.

Gouty arthritis Management of gouty arthritis Gout is defined by the deposition of monosodium urate crystals in various tissues, which is usually the result of hyperuricaemia. However, it should be noted that while the majority of patients who develop gout have been hyperuricaemic for about two decades, the majority of individuals with hyperuricaemia never develop gout [1] and may not require treatment. Gout may manifest as one or more of the following clinical syndromes: gouty arthritis, subcutaneous tophaceous deposition, gouty nephropathy and uric acid nephrolithiasis. Overall, the prevalence of gout increases with age and serum urate concentrations. It primarily affects middle-aged men. In the Framingham study reported in 1988 [1], the overall 2-year incidence of gout was found to be 0.32% in men and 0.05% in women, with a mean age of 58 years. Using a selfreported questionnaire, the estimated prevalence of gout was found to be 0.84% for all ages; with the highest prevalence reported in people over age 65 (2.9%) [45]. The prevalence of gout parallels that of hyperuricaemia, which varies with age, sex, body mass index, renal function, and ingestion of alcohol and drugs. Drugs that are responsible for hyperuricaemia and gout include diuretics, cyclosporin A, low-dose salicylates, ethambutol, pyrazinamide and nicotinic acid. Gout is more prevalent in industrialised countries and is a growing problem worldwide. Acute gouty arthritis is generally the first clinical manifestation of gout. It may be triggered by a specific event such as trauma, alcohol, drugs (particularly diuretics), surgical stress, or acute medical illness. Early episodes of acute gouty arthritis are typically monoarticular and begin abruptly, often during the night or early morning escalating over a 6- to 12-hour period. There is severe pain, erythema and swelling, as well as systemic features such as fever and chills. The joints of the lower limbs are typically involved and the first metatarsophalangeal joint is involved in >50% of initial attacks and over time is affected in >90% of patients. The shoulder, hip and axial joints are rarely affected. Early attacks often spontaneously resolve over 3 to 10 days, although

subsequent attacks can occur more frequently, become polyarticular and persist longer. The transition from acute intermittent gout to chronic tophaceous gout develops over 10 years or more. This transition is characterised by the intercritical periods between gouty attacks becoming less defined, diminished in intensity of the pain and persistent joint abnormalities [37]. The detection of intra- or extra-cellular needleshaped negatively birefringent urate crystals on a polarised microscopic examination of synovial fluid establishes the diagnosis of acute gouty arthritis. The fluid is inflammatory — typically 20,000–100,000 white cells per mm2, with a predominance of neutrophils. Serum uric acid levels will be elevated at some time in almost all patients with gout, but the level can be normal at the time of an acute gouty attack and should not be relied on to formulate a diagnosis. A full blood count may show an elevated ESR, mild neutrophil leucocytosis, and possibly reactive thrombocytosis. Infective arthritis is an important differential diagnosis of acute gout since systemic features and leucocytosis are common to both conditions, and septic synovial fluids may contain urate crystals. Synovial fluid cultures should therefore be obtained if a clinical suspicion of a septic joint exists. In the absence of microscopic urate crystal identification, the presumptive diagnosis of gout can be made using clinical criteria as has been defined by the ACR (Table 16.06) [54].

Table 16.06 Diagnosis of acute gouty arthritis in the absence of microscopic urate identification • History of more than one attack of acute arthritis • Maximum inflammation developed within 1 day • Monoarticular attack • Unilateral first metatarsophalangeal arthritis • Unilateral tarsal arthritis • Tophus (proven or suspected) • Hyperuricaemia • Asymmetrical swelling within a joint on X-ray • Subcortical cysts without erosions on X-ray • Joint fluid culture negative for organisms during attack Adapted from the 1977 American College of Rheumatology Preliminary Criteria for classification of acute arthritis of primary gout [54].

Painful Arthritis and Rheumatic Conditions 267

Non-steroidal anti-inflammatory drugs and colchicine are effective in the treatment of acute gouty arthritis. Potent NSAIDs such as indomethacin, used at regular anti-inflammatory doses, are generally recommended until the attack subsides. However, if GI intolerance is a concern, recent studies have shown that the COX-2 inhibitors are equally effective as indomethacin in the treatment of acute gout [67, 90]. Colchicine inhibits leucocyte activation and migration and is most effective when given in the first 24 to 48 hours of the attack. However, side effects such as nausea, abdominal pain and diarrhoea are common and limit its use. It is relatively contraindicated in patients with renal insufficiency. In patients with contraindications to NSAIDs and colchicines or with acute gouty arthritis that is refractory to these therapies, glucocorticoids may be used. In the case of monoarthritis, intra-articular injections may be the treatment of choice. Oral or intramuscular glucocorticoids may be considered when patients decline arthrocentesis or present with oligo- or polyarticular gout. Drugs such as allopurinol and probenecid that alter serum uric acid levels should not be started until after complete resolution of the acute gouty attack, nor should they be stopped if an acute gouty attack occurs while the patient is on these medications. The long-term management of gout consists of lifestyle modification and avoidance of use of drugs that may induce gout. Patients should be advised to limit their intake of purine-rich foods such as meats, seafood, some vegetables and legumes. They should also be strongly advised against the use of alcohol. Uric acid lowering agents include two classes of drugs: the xanthine oxidase inhibitors, which block

Table 16.07

Indications for long-term uric acid lowering agents

• Frequent and disabling attacks of acute gouty arthritis • Clinical or radiographic signs of chronic gouty joint disease • Presence of tophaceous deposits in soft tissues or subchondral bone • Gout with renal insufficiency • Recurrent nephrolithiasis • Excessive urinary uric acid excretion • Impending cytotoxic chemotherapy or radiotherapy for lymphoma or leukaemia

uric acid synthesis, and the uricosurics, which increase renal uric acid secretion. In general, uric acid lowering agents should be used judiciously as these drugs are costly, inconvenient and potentially toxic, and should not be offered to patients with asymptomatic hyperuricaemia [40]. Indications for long-term use of these drugs are listed in Table 16.07. Allopurinol is the classical xanthine oxidase and has been the mainstay of treatment of chronic gout in the last few decades, although it often fails to adequately reduce uric acid level and prevent recurrent gouty attacks. In recent years, a number of new agents have become available. Febuxostat is a new xanthine oxidase inhibitor which has been shown to be an effective hypouricaemic agent, although its use in patients with renal impairment and other significant medical conditions requires further evaluation. Other novel agents include uricase, which catalyses the conversion of uric acid to the more readily excreted allantoin. Rasburicase is a recombinant uricase, which has recently been approved for the prevention of tumour lysis syndrome although its use in chronic gout is limited by antigenicity. A less antigenic PEGylated uricase is currently being evaluated although further information with regard to its long-term risks and benefits is required. It is possible that uricases may in the future be used as inducing agents to rapidly deplete uric acid stores in the short term. This will then be followed by long-term maintenance therapy with a hypouricaemic agent to prevent subsequent accumulation of uric acid and recurrent gouty attacks [79]. Uricosuric agents include probenecid and benzbromarone, but their use is limited by their low efficacy in patients with renal impairment.

Periarticular and regional rheumatic pain syndromes Management of common soft tissue rheumatism Periarticular and regional rheumatic pain syndromes are also known as STR syndromes. These conditions are commonly overlooked in the planning of the medical curriculum and that of the provision of health care. Yet single or multiple lesions of tendons and their sheaths, fasciae, bursae, joint capsules and the enthesis (the tenoperiosteal junction) are major causes of work days lost in the community [83], as

268 Chak Sing LAU

well as rheumatology work load comprising up to 43% of new patient referrals [5]. Most STR conditions are related to chronic low-grade trauma as a result of excessive and/or unaccustomed use both at work and at play. The conditions cause partial interruption of the blood supply leading to incomplete attempts at healing and regeneration. Since the vascular supply to adult tendon is poor, healing of these lesions is slow. The middle-aged and the elderly are especially vulnerable, and in whom these lesions predominate. Periarticular and regional rheumatic pain syndromes may also be associated with systemic diseases, notably inflammatory arthropathies, such as RA and AS, and diabetes mellitus as one of the clinical sequelae of a generalised vasculopathy associated with this condition. A neural theory as a possible cause of STR syndromes has also been proposed recently based on the observations that tendons are innervated and that increased levels of substance P, a nociceptive neurotransmitter which has been implicated as a proinflammatory mediator, have been found in rotator cuff tendonitis. Further, glutamate, a neurotransmitter, has been found within the ultradialysate in Achilles tendonitis. Finally, an association between radiculopathy and tendon disorders has been reported recently [65]. The diagnosis of STR syndromes relies largely on the physician’s clinical acumen and laboratory tests; radiological techniques are often not needed. Much can be done once the diagnosis is made as STR often responds to a range of treatments including selective rest of the involved region, use of oral and topical analgesics and anti-inflammatory drugs, physiotherapy and intralesional infiltration of glucocorticoid. The clinical presentation and diagnosis of common STR syndromes are summarised in Table 16.08. Although, numerous forms of treatment are available for STR syndromes, few, unfortunately, have been studied in a controlled and prospective manner and their use remains controversial. Experience with the use of NSAIDs in STR syndromes is not always positive and most feel these agents work through

their analgesic rather than anti-inflammatory effects. Various forms of physical therapy have been used to treat STR syndromes. They include cryotherapy, therapeutic ultrasound and manual therapy, such as deep transverse friction massage and eccentric training, which involves active lengthening of the muscle tendon unit [65]. While intralesional glucocorticoid injection is not proven, it is commonly offered when conservative treatment fails. Table 16.08 describes also the injection site and recommended dose of glucocorticoids used in common STR syndromes.

Conclusion In conclusion, arthritis and rheumatic diseases encompass a wide spectrum of syndromes ranging from degenerative diseases such OA to immune mediated deforming conditions such as RA and AS, and remediable conditions such as some cases of gout and STR syndromes. They are major causes of pain, physical disability and socioeconomic loss in developed countries. This is underlined by the WHO’s declaration of the years 2000–2010 the Bone and Joint Decade. Management of these conditions requires an in-depth knowledge of the underlying pathology and the various modalities of treatment available. It requires a multidisciplinary approach involving many medical and non-medical personnel. The use of drugs has a major role in the treatment of chronic arthritis. The ideal drug should provide symptomatic relief and eradicate the underlying condition without causing side effects. While such a drug(s) is not yet available and there is still no cure, progress made in recent years in our understanding of arthritis and the mechanism of actions of anti-rheumatic drugs has provided much hope for patients with rheumatic diseases. It is now possible to keep arthritis symptoms under good control with judicious use of therapeutic agents that are well tolerated. In addition, thanks to research advances in the immunopathology of conditions such as RA and AS, some previously treatment refractory diseases may now respond to the use of biological agents. These agents may also induce a prolonged remission in patients with early disease.

Painful Arthritis and Rheumatic Conditions 269

Clinical features and glucocorticoid injection site/dose of common soft tissue rheumatism syndromes Injection site and steroid dose (in mg methylprednisolone or equiv.)

Wrist and hand region

Elbow region

Soft tissue syndrome Presenting feature(s) Physical findings Shoulder region

Table 16.08

Supraspinatus

Pain in deltoid region during shoulder abduction and at night when lying on the affected side

Normal passive shoulder movement. Painful arc (70–120o) during active abduction and a “catch” of pain as the shoulder is lowered. Resisted shoulder abduction increases pain

Anterior edge of the acromion with the forearm resting on the thigh, or with the elbow bent at 90o and the forearm placed behind the back (20–40 mg)

Infraspinatus

As for supraspinatus tendonitis

As for supraspinatus tendonitis but pain increase is elicited during resisted shoulder external rotation

Posterior to the acromial head with the patient sitting upright or lying face downwards, propped up on their elbows (20–40 mg)

Biceps tendonitis

Often associated with rotator cuff tendonitis. Pain over the anterior aspect of the shoulder with radiation into the biceps muscle during overhead activities

Tenderness over the tendon as it runs in the bicipital groove

Along the biceps tendon (AVOID DIRECT INJECTION) (20–40 mg)

Subacromial bursitis

Often associated with rotator cuff tendonitis with similar symptoms

Passive shoulder movement may be limited. Resisted abduction is painful from 45–90o. Passive rotation of the shoulder in the fully abducted position may be painful

Mid-point of the subacromion laterally. Aspirate any excess fluid (20–40 mg)

Lateral Pain over lateral epicondylitis epicondyle. Hand (Tennis elbow) grip may be impaired

Lateral epicondyle tenderness. Worse by resisted wrist extension with the elbow extended

Over the lateral epicondyle (20 mg)

Medial epicondylitis (Golfer’s elbow)

Pain over medial epicondyle. Hand grip may be impaired

Medial epicondyle tenderness. Worse by resisted wrist flexion with the elbow extended

Over the medial epicondyle. KEEP INJECTION ANTERIOR TO AVOID ULNAR NERVE DAMAGE (20 mg)

de Quervain’s tenosynovitis (Diaper wrist)

Pain on using the thumb or wrist

Maximal tenderness in the anatomical “snuff box”. Visible tender swelling over the radial styloid

Site of maximum tenderness. AVOID DIRECT INJECTION. Avoid long acting steroids (25–50 mg)

Carpal tunnel syndrome

Pain and paraesthesia of the lateral 3 1/2 fingers. Worse in the morning and relieved by shaking the hand/forearm

Arm elevation or hyperflexion of the wrist produces pain and paraesthesia. Tinel’s test may be positive. There may be thenar eminence wasting

Midpoint between the pisiform and scaphoid tubercle distal to the middle skin crease. Needle is directed at ~60o to the forearm. AVOID LOCAL ANAESTHETICS (20–40 mg)

270 Chak Sing LAU

Foot and ankle region

Soft tissue syndrome Presenting feature(s) Physical findings

Injection site and steroid dose (in mg methylprednisolone or equiv.)

Stenosing digital tenosynovitis (Trigger finger)

Triggering of the affected finger

Pain during resisted finger Over the involved tendon sheath. flexion and on stretching AVOID DIRECT INJECTION the tendon passively (12–20 mg) in extension. A tender nodule may also be felt

Achilles’ tendonitis

Painful Achilles tendon during walking

Localised tenderness +/- nodular or diffuse swelling

INJECTION BEST AVOIDED

Plantar fasciitis

Pain on the undersurface of the heel on weight bearing. Worse after immobility

Localised tenderness, without swelling, over the anteromedial portion of the plantar surface of the calcaneum. Passive dorsiflexion of the toes worsens pain

From the side of the plantar fascia around the point of maximum tenderness. AVOID DIRECT INJECTION (20–40 mg)

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

Abbott RD, Brand FN, Kannel WB, et al. Gout and coronary artery disease: The Framingham study. J Clin Epidemiol 1988;41:237–42. Abdel-Nasser AM, Rasker JJ, Valkenburg HA. Epidemiological and clinical aspects relating to the variability of rheumatoid arthritis. Sem Arthritis Rheum 1997;27:123–40. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum 2000;43:1905–15. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;30:315–24. Bamji AN, Dieppe PA, Haslock DI, et al. What do rheumatologists do? A pilot audit study. Br J Rheumatol 1990;29:295– 8. Baraliakos X, Landewe R, Hermann KG, et al. Inflammation in ankylosing spondylitis: A systemic description of the extent and frequency of acute spinal changes using magnetic resonance imaging. Ann Rheum Dis 2005;64:730–4. Barthon JM, Martin RW, Felischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343:1586–93. Boers M. Rheumatoid arthritis. Treatment of early disease. Rheum Dis Clin North Am 2001;27:405–14. Bombardier C, Laine L, Reicin A, et al. VIGOR-study-Group. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000;343(21):1520–8. Braun J, Bollow M, Remlinger G, et al. Prevalence of spondyloarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 1998;41:58–67. Braun J, Brandt J, Listing J, et al. Treatment of active ankylosing spondylitis with infliximab: A randomised controlled multicentre trial. Lancet 2002;359:1187–93. Brooks PM. The burden of musculoskeletal disease — a global perspective. Clin Rheumatol 2006;25:778–81. Chen J, Liu C. Sulfasalazine for ankylosing spondylitis. Cochrane Database Syst Rev 2005;2:CD004800. Chopra A, Saluja M, Patil J, et al. Pain and disability, perceptions and beliefs of a rural Indian population: A WHO/ ILAR/COPCORD study. J Rheumatol 2002;9:614–21. Cohen MG, Li EK, Ng PY, et al. Extra-articular manifestations are uncommon in southern Chinese with rheumatoid arthritis. Br J Rheumatol 1993;32:209–11. Cohen S, Cannon GW, Schiff M, et al. Two-year, blinded, randomized, controlled trial of treatment of active rheumatoid arthritis with leflunomide compared with methotrexate. Arthritis Rheum 2001;44:1984–992. Dagfinrud H, Kvien TK, Hagen KB. The Cochrane review of physiotherapy interventions for ankylosing spondylitis. J Rheumatol 2005;32:1899–906. Darmawan J, Valkenburg HA, Muirden KD, et al. Epidemiology of rheumatic diseases in rural and urban populations in Indonesia. A WHO/ILAR/COPCORD study, Stage 1, Phase 2. Ann Rheum Dis 1992;51:525–8.

Painful Arthritis and Rheumatic Conditions 271

19. Davis JC Jr, van der Heijde D, Braun J, et al. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: A randomized, controlled trial. Arthritis Rheum 2003;48:3230–6. 20. Decker JL. Glossary Subcommittee of the ARA Committee on Rheumatologic Practice. Arthritis Rheum 1983;26:1029– 32. 21. Doherty M, Watt I, Dieppe P. Influence of primary generalized osteoarthritis on development of secondary osteoarthritis. Lancet 1983;11:8–11. 22. Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;350:2572–81. 23. Emery P, Breedveld FC, Dougados M. Early referral recommendation for newly diagnosed rheumatoid arthritis: Evidence-based development of a clinical guide. Ann Rheum Dis 2002;61:290–7. 24. Firestein GS. Etiology and pathogenesis of rheumatoid arthritis. In Ruddy S, Harris ED, Sledge CB, Kelly WN, eds. Kelly’s Textbook of Rheumatology, 7th edn. Philadelphia: WB Saunders, 2005:996–1042. 25. Geijer M, Sihlbom H, Gothlin JH, et al. The role of CT in the diagnosis of sacro-iliitis. Acta Radiol 1998;39:265–8. 26. Genovese MC, Becker JC, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 2005;353:1114–23. 27. Graham DJ, Campen D, Hui R, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase-2 selective and non-selective non-steroidal anti-inflammatory drugs: Nested case-control study. Lancet 2005;365:475–81. 28. Haibel H, Brandt J, Rudwaleit M, et al. Treatment of active ankylosing spondylitis with pamidronate. Rheumatol 2003;42:1018–20. 29. Harkness EF, Macfarlane GJ, Silman AJ. Is musculoskeletal pain more common now than 40 years ago?: Two population based cross-sectional studies. Rheumatol 2005;44:890–5. 30. Hasselstrom J, Liu-Pal M, Gren J, et al. Prevalence of pain in general practice. Eur J Pain 2002;6:375–85. 31. Higashida J, Wun T, Schmidt S, et al. Safety and efficacy of rituximab in patients with rheumatoid arthritis refractory to disease modifying antirheumatic drugs and anti-tumor necrosis factor-alpha treatment. J Rheumatol 2005;32:2109– 15. 32. Ho CTK, Lau CS. Intralesional steroid injections — general considerations. The Hong Kong Practitioner 1997;19:425– 9. 33. Hochberg MC. Role of intra-articular hyaluronic acid preparations in medical management of osteoarthritis of the knee. Semin Arthritis Rheum 2000;30(Suppl):2–10. 34. Huang F, Gu J, Zhao W, et al. One-year open-label trial of thalidomide in ankylosing spondylitis. Arthritis Rheum 2002;47:249–54. 35. Jordan KM, Arden NK, Doherty M, et al. EULAR Recommendation 2003: An evidence-based approach to the management of knee osteoarthritis: Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 2003;62:1145–55. 36. Kearney PM, Baigent C, Godwin J, et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal antiinflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 2006;332:1302–8. 37. Keith MP, Gilliland WR. Updates in the management of gout. Am J Med 2007;120:221–4. 38. Kirwan JR. Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med 1995;333:142–6. 39. Koopman WJ, Schronhenberg RE. Rheumatoid factor. In Utsinger PD, Zvaifler NJ, Ehrlich GE, eds. Rheumatoid Arthritis: Etiology, Diagnosis and Therapy. Philadelphia: JB Lippincott, 1985. 40. Laing MH, Fries JF. Asymptomatic hyperuricaemia. The case for conservative management. Ann Intern Med 1978;88:666–70. 41. Lau CS. Diseases of joints and bones. In Forbes CD and Jackson WF, eds. A Colour Atlas and Text of Clinical Medicine, 1st edn. London: Wolfe, 1993:121–60. 42. Lau CS, Vargas B, Louthreeno W, et al. Features of spondyloarthritis around the world. Rheum Dis Clin N Am 1998;24(4):753–70. 43. Lau E, Symmons D, Bankhead C, et al. Low prevalence of rheumatoid arthritis in the urbanized Chinese of Hong Kong. J Rheumatol 1993;20(7):1133–7. 44. Lauhio A, Leirisalo-Repo M, Lahdevirta J, et al. Double blind, placebo controlled study of three months treatment with lymecycline in reactive arthritis, with special reference to Chlamydia arthritis. Arthritis Rheum 1991;24:6–14. 45. Lawrence RA, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998;41:778–89. 46. Lee KW, Lau CS. Regional steroid injections — Intra-articular injections. The Hong Kong Practitioner 1997;19:482–9. 47. Lichenstein D, Syngal S, Wolfe MM. Non-steroidal anti-inflammatory drugs and the gastrointestinal tract: The doubleedged sword. Arthritis Rheum 1995;38:5–18. 48. Lipsky PE, van der Heijde DM, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med 2000;343:1594–602.

272 Chak Sing LAU 49. MacGregor AJ, Snieder H, Rigby AS, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum 2000;43:30–7. 50. Maksymowych WP, Jhangri GS, Fitzgerald AA, et al. A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of non-steroidal anti-inflammatory drug-refractory ankylosing spondylitis. Arthritis Rheum 2002;46:766–73. 51. Manahan L, Caragay R, Muirden KD, et al. Rheumatic pain in a Philippine village. A WHO/COPCORD study. Int J Rheumatol 1985;5:149–53. 52. Mansour M, Cheema GS, Naguwa SM, et al. Ankylosing spondylitis: A contemporary perspective on diagnosis and treatment. Sem Arthritis Rheum 2007;36:210–23. 53. March LM, Bachmeier CJM. Economics of osteoarthritis: A global perspective. Ballieres Clin Rheumatol 1997;11:817– 34. 54. Masi H, Decker AT, McCarty JL, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895–900. 55. Mathers C, Penm R. Health system costs of injury, poisoning and musculoskeletal disorders in Australia 1993–94. Canberra, Australian Institute of Health and Welfare, 1999 (AIHW Catalogue No. HWE 12; Health and Welfare Expenditure Series No. 6). 56. Moreland LW. Biologic therapies on the horizon for rheumatoid arthritis. J Clin Rheumatol 2004;10(Suppl):S32–39. 57. Murray CJL, Lopez AD, eds. The Global Burden of Disease. A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Cambridge, MA: Harvard School of Public Health on behalf of the World Health Organization and The World Bank, 1996. 58. Needleman P, Isakson PC. The discovery and function of COX-2. J Rheumatol 1997;246–8. 59. Nuki G, Breshnihan B, Bear MB, et al. Long-term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin-1 receptor antagonist) in patients with rheumatoid arthritis: Extension phase of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002;46:2838–46. 60. Olsen NJ, Stein CM. New drugs for rheumatoid arthritis. N Engl J Med 2004;350:2167–79. 61. Paulus HE. FDA arthritis advisory committee meeting: Serious gastrointestinal toxicity of non-steroidal antiinflammatory drugs, etc. Arthritis Rheum 1988;31:1450–1. 62. Petrella RJ. Hyaluronic acid for the treatment of knee osteoarthritis: Long term outcomes from a naturalistic primary care experience. Am J Phys Med Rehabil 2005;84:278–83. 63. Picavet HS, Schouten JS. Musculoskeletal pain in the Netherlands: Prevalences, consequences and risk groups, the DMC (3) study. Pain 2003;102:167–78. 64. Pincus T, O’Dell JR, Kremer JM. Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis: A preventive strategy. Ann Intern Med 1999;131:768–74. 65. Rees JD, Wilson AM, Wolman RL. Current concepts in the management of tendon disorders. Rheumatol 2006;45:508– 21. 66. Reginister JY, Bruyere O, Neuprez A. Current role of glucosamine in the treatment of osteoarthritis. Rheumatol 2007;46:731–5. 67. Rubin BR, Burton R, Navarra S, et al. Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: A randomized controlled trial. Arthritis Rheum 2004;50:598–606. 68. Rudwaleit M, van der Heijde D, Khan MA, et al. How to diagnose axial spondyloarthritis early. Ann Rheum Dis 2004;63:535–43. 69. Sambrook P, Cooper C. Osteoporosis. Lancet 2006;367:2010–8. 70. Sieper J, Braun J, Rudwaleit M, et al. Ankylosing spondylitis: An overview. Ann Rheum Dis 2002;61(Suppl 3):iii8– iii18. 71. Silman AJ, Hochberg MC. Epidemiology of the Rheumatic Diseases. Oxford: Oxford University Press, 1993. 72. Silman AJ, Ollier W, Holligan S, et al. Absence of rheumatoid arthritis in a rural Nigerian population. J Rheumatol 1993;20:618–22. 73. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs non-steroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: The CLASS study: A randomized controlled trial. Celecoxib Longterm Arthritis Safety Study. JAMA 2000;284(10):1247–55. 74. Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving non-steroidal anti-inflammatory drugs: A randomised, double-blind, placebo controlled trial. Ann Intern Med 1995;123:241–9. 75. Singh G, Ramey DR, Morfeld D, et al. Gastrointestinal tract complications of non-steroidal anti-inflammatory drug treatment in rheumatoid arthritis: A prospective observational cohort study. Arch Intern Med 1996;156:1530–6. 76. Solomon DH, Glynn RJ, Levin R, et al. Non-steroidal anti-inflammatory drug use and acute myocardial infarction. Arch Intern Med 2002;162:1099–104.

Painful Arthritis and Rheumatic Conditions 273 77. Solomon SD, McMurray JJV, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005;352:1071–80. 78. Spector TD, Hart DJ, Powell RJ. Prevalence of rheumatoid arthritis and rheumatoid factor in women: Evidence for a secular decline. Ann Rheum Dis 1993;52:54–7. 79. Stamp LK, O’Donnell JL, Chapmann PT. Emerging therapies in the long-term management of hyperuricaemia and gout. Int Med J 2007;37:258–66. 80. Symmons D, Harrison B. Early inflammatory polyarthritis: Results from the Norfolk Arthritis Register with a review of the literature. I. Risk factors for the development of inflammatory polyarthritis and rheumatoid arthritis. Rheumatol 2000,39:835–43. 81. Tepper S, Hochberg MC. Factors associated with hip osteoarthritis: Data from the First National Health and Nutrition Examination Survey (NHANES-I). Am J Epidemiol 1993;137:1081–8. 82. The 51st World Health Assembly. Geneva, Switzerland. 11–16 May 2008. 83. Urwin M, Symmons D, Alison T, et al. Estimating the burden of musculoskeletal disorders in the community: The comparative prevalence of symptoms at different anatomical sites, and the relationship to social deprivation. Ann Rheum Dis 1998;57:649–55. 84. van der Heijde D, Kivitz A, Schiff M, et al. Adalimumab therapy results in significant reduction of signs and symptoms in subjects with ankylosing spondylitis: The ATLAS trial. Arthritis Rheum 2006;54:2136–46. 85. van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, et al. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: Clinical efficacy, disease-modifying properties, and side effects. Ann Intern Med 2002;136:1–12. 86. van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: A prospective cohort study. Arthritis Rheum 2004;50:709–15. 87. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of actions for aspirin-like drugs. Nature 1971;231:232– 9. 88. Wanders A, Heijde D, Landewe R, et al. Non-steroidal anti-inflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: A randomised clinical trial. Arthritis Rheum 2005;52:1756–65. 89. Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: The ARMARDA trial. Arthritis Rheum 2003;48:35–45. 90. Willburger RE, Mysler E, Derbot J, et al. Lumiracoxib 400 mg once daily is comparable to indomethacin 50 mg three times daily for the treatment of acute flares of gout. Rheumatology 2007;46:1126–32. 91. World Health Organization. Life in the 21st Century — A Vision for All. The World Health Report, 1998. 92. World Health Organization. The burden of musculoskeletal conditions at the start of the new millennium. WHO Technical Report Series 2003;919:i-x, 1–218. 93. Zhang W, Doherty M, Arden N, et al. EULAR Recommendation 2003: An evidence-based approach to the management of hip osteoarthritis: Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 2005;64:669–81.

17

Simon K.C. CHAN, Alice K.Y. MAN

Pain Associated with Medical Diseases

INTRODUCTION PAIN AND ENDOCRINE DISEASE Diabetes mellitus PAIN AND CARDIOVASCULAR DISEASES Peripheral arterial disease Coronary artery disease Non-cardiac chest pain PAIN AND INFECTIOUS DISEASES Human immunodeficiency virus disease Severe Acute Respiratory Syndrome PAIN AND HAEMATOLOGICAL DISORDERS Haemophilia Sickle cell disease PAIN AND PANCREATIC DISORDERS Acute pancreatitis Chronic pancreatitis Pancreatic cancer VISCERAL PAIN Functional gastrointestinal disorders Chronic pelvic pain

Introduction Pain is traditionally regarded as a sign of disease and the function of the pain sensory system is to detect, localise and identify tissue-damaging processes in order to protect and maintain the body’s homeostasis. Hence, pain is the most common symptom that leads a patient to seek medical advice [26]. In most situations, the appropriate treatment is to limit the disease process and the pain will be alleviated. However, in some situations in which definitive treatment is lacking, such as human immunodeficiency virus (HIV) disease, patients continue to suffer severe chronic pain despite the correct diagnosis having been made. Pain management thus becomes an integral part of the overall patient care in order to improve the quality of life. Different aetiologies and pathological processes mean that different diseases produce different pain syndromes, and an understanding of the underlying pathophysiology of each disease as well as its related pain syndrome is important in managing these patients.

Pain and Endocrine Disease Diabetes mellitus Background Diabetes mellitus (DM) is a common disease which affects multiple organ systems, such as the cardiovascular, renal, peripheral nervous system and the eye. In the setting of the pain clinic, pain physicians are likely to be involved in the care of diabetic patients with diabetic peripheral neuropathic pain (DPNP) or peripheral vascular disease and its related complications. Diabetic peripheral neuropathy (DPN) is a disorder that is characterised by signs and symptoms of peripheral nerve dysfunction in patients with DM in

276 Simon K.C. CHAN, Alice K.Y. MAN

whom other causes of peripheral neuropathy are excluded. Although most patients with DPN do not experience pain, pain associated with DPN significantly impairs the quality of life in diabetic patients [7].

Epidemiology In 2000, it was estimated that 150 million people worldwide were suffering from DM and that the number would double by the year 2025 [97]. The incidence of DM is higher in the developed world; 20.8 million people (or 7% of the overall population) in the United States have DM [7]. The prevalence of DM is related to the ageing population and excess weight gain. In Hong Kong, the prevalence of DM in the elderly (over 50 years of age) was found to be 15–20% [94]. Depending on the sampled population, the prevalence of DPN in diabetic patients ranged from 20–60% in a recent review [69]. Among those with type I and type II DM, 54% and 45% respectively had DPN [7]. However, not all patients with DPN have symptoms. Up to 50% of patients with DPN experience some degree of pain and of these, 10–20% have symptoms severe enough to seek treatment [7]. Because of the different definition of DPNP, its prevalence varies from 11–20% and the number of people suffering pain from DPN ranges from 600,000 to 3.6 million in the United States [7].

5. Auto-immune mechanism 6. Nerve growth hormone (neurotrophins) deficiency leading to axonal atrophy. Irrespective of the mechanism, neuronal, axonal and Schwann cell metabolism are deranged leading to impaired axonal transport and neuronal dysfunction.

Clinical Features Diabetes-associated neuropathies can manifest as generalised symmetrical polyneuropathies and focal or multifocal neuropathies. A classification of diabetic neuropathy based on the clinical features, which are either symmetrical or asymmetrical, has been summarised by Bansal et al. [11]. The symmetrical neuropathies include: diabetic polyneuropathy, painful autonomic neuropathy and painful distal neuropathy; asymmetrical neuropathies include: radiculoplexoneuropathies such as lumbosacral, thoracic, cervical and cranial neuropathy, and asymmetric proximal diabetic neuropathy, previously known as diabetic amyotrophy.

Pathophysiology The pathophysiology of diabetic neuropathy remains unclear, but the incidence of DPN is more frequent with increasing age and duration of DM, as well as the duration and severity of exposure to hyperglycaemia. The pathogenesis of diabetic neuropathy is multifactorial and a number of mechanisms have been proposed [75]:

Although various neuropathies have been described, DPN (also known as chronic sensorimotor distal symmetrical polyneuropathy) accounts for 75% of diabetes-associated neuropathies. Both small and large nerve fibres can be affected in DPN, which impairs both sensory and motor function. However, impairment of motor function is usually mild; pronounced motor signs or asymmetrical distribution would suggest a non-diabetic cause of neuropathy. The small fibre disease may be associated with diabetic autonomic neuropathy as well. Diabetic peripheral neuropathy is insidious in onset and usually affects the feet and lower limbs first, with the hands affected later, in a “stocking and glove” distribution.

1. Metabolic — activation of the polyol pathway and the resultant reduction in Na+/K+-ATPase activity 2. Non-enzymatic glycation leading to glycosylation and changes in proteins in nerve fibres 3. Vascular — hyperglycaemia, thought by way of activation of protein kinase C to result in a poor blood supply to and even infarction of the nerves 4. Oxidative stress — reduced blood supply to nerve fibres leads to free radical formation

The symptoms of DPN may be spontaneous or evoked and are usually worse at night. The pain (“positive symptoms”) which occurs in 11–20% of DPN can be of type C fibre (lancinating, burning and dysaesthetic) or A-delta type (deep seated, dull and gnawing). Patients may also experience “negative symptoms” such as numbness or a “dead” feeling in their feet. Unsteadiness, which may be secondary to abnormal proprioception or muscle sensory function, is also seen. The presence of clinical features such as tachycardia, painless myocardial infarction, orthostatic hypotension,

Pain Associated with Medical Diseases 277

oesophageal dysfunction, gastroparesis, diarrhoea, constipation, incontinence, erectile dysfunction, neurogenic bladder, and dry and warm feet would indicate autonomic neuropathy.

conduction velocity diminishes gradually in diabetic neuropathy by 0.5 m/s/year. Autonomic function tests are based on specific manoeuvres for variation in blood pressure and heart rate.

Acute sensory neuropathy is rare; it tends to occur after a period of metabolic instability, such as ketoacidosis or poor glycaemic control, and is characterised by pain with few clinical signs. The blood glucose level correlates with pain symptoms and a return to euglycaemia often results in resolution of pain. Sometimes acute diabetic neuropathic pain associated with weight loss and depression is called diabetic neuropathic cachexia.

The American Academy of Neurology has recommended that diabetic neuropathy be diagnosed in the presence of somatic or autonomic neuropathy when other diagnoses have been excluded (Table 17.01) [1].

During the progression of disease, patients develop tolerance to medical therapy and chronic diabetic neuropathy results. Patients with chronic diabetic neuropathy are susceptible to foot injury and ulcer, which can cause significant morbidity. The natural history of DPN and DPNP is largely unknown with conflicting reports [7]. It has been reported that symptoms of DPNP decreased after 3.6 years, but there was no change in pain severity after 5 years in another study. Moreover, pain symptoms and nerve conduction velocity were reported to decline at 1 year follow-up.

Diagnosis The diagnosis of DPN is made clinically and is based on history, physical examination and investigations. Physical examination including muscle power and sensation (pin prick, vibration with 128Hz tuning fork and temperature) is essential. The common finding is symmetrical loss of sensation in a stocking distribution. The presence of asymmetrical motor deficit highly suggests a non-diabetic cause of neuropathy [13]. Signs of autonomic neuropathy like warm and dry skin may be present. Regular examination of the feet in diabetic patients is essential. Plantar callosities, foot ulcer, pes cavus and clawed toes represent a picture of the diabetic foot. The presence of unilateral heat and swelling in a neuropathic diabetic foot suggests acute Charcot neuropathy [69]. Nerve conduction study changes in diabetic neuropathy are non-specific and aim at excluding other important differential diagnoses like entrapment and nerve demyelination. The nerve

Management Once a diagnosis of DPN has been made, the patient should have the disease explained, including its prognosis and treatment goals, so that a a good rapport and an effective management plan can be established. There are three aspects to the management of DPN: disease modification, symptomatic relief and prevention of complications. 1. Disease modification Secondary preventive measures, including treatment of hypertension and hyperlipidaemia, and good glycaemic control can substantially reduce the risk of developing complications and slow their progression in all types of DM. Glycaemic control aims at maintaining glycated haemoglobin (HbA1c) at less than 6%; appropriate measures include: diet; exercise; oral hypoglyacaemic agents; and insulin administration. Intensive insulin therapy can reduce the prevalence of diabetic neuropathy by 50% [2]. In addition, carnitine has been shown to improve sural nerve fibre number and vibration perception, as well as pain control [74]. Table 17.01 Non-diabetic causes of peripheral neuropathy Causes

Example

Malignancy

Carcinoma of lung

Nutritional deficiency

Vitamin B12 deficiency

Toxins

Alcohol

Infection

Human immunodeficiency virus

Drugs

Vinca alkaloids, isoniazid, chemotherapy

278 Simon K.C. CHAN, Alice K.Y. MAN

2. Symptomatic Relief A number of pharmacological agents with different mechanisms of action have been shown to be effective for neuropathic pain with variable efficacy. Recently, consensus guidelines specifically for the treatment of DPNP based on evidence from clinical trials have been developed [6]. Drug treatment of DPNP has been ranked in three categories: firsttier, second-tier and “honorable mention”. (a) First-tier agents Four agents or class of agents have been ranked in this category. • Duloxetine — a serotonin-noradrenaline reuptake inhibitor (SNRI) is one of the only two agents approved by the Food and Drug Administration (FDA) for the treatment of DPNP. The recommended dosage is 60–120 mg/day; adverse effects, such as somnolence and constipation are manageable. • Pregabalin — an anticonvulsant and the second drug approved by the FDA for treatment of DPNP. The recommended dose for DPNP is 300–600 mg/day; side effects, which include somnolence and dizziness, can be troublesome at that dosage. • Oxycodone CR — a long-acting opioid that has been shown to be effective in swelldesigned clinical trials. Adverse effects are similar to other opioids; the starting dose of 20mg/day can be increased to 60 mg. • Tricyclic antidepressants — the number needed to treat (NNT) of amitriptyline for the treatment of DPNP has been shown to be 1.3 in the Cochrane collaborative analysis, but wide clinical use of tricyclic antidepressants is limited by their adverse effects. (b) Second-tier agents This tier of agents was recommended based on the positive results of both a randomised controlled trial (RCT) for DPNP and RCTs for treatment of other neuropathies. Five agents have been ranked in this category: carbamazepine, gabapentine, lamotrigine (an anticonvulsant with antidepressant properties), tramadol and venlafaxine ER (an SNRI). Please refer to Chapters 21 and 23 for their pharmacology. (c) Others (“honourable mention” category) Recommendations in this category were based on positive results of RCTs for treatment

of other neuropathies and include: topical agents (capsaicin and lignocaine), bupropion, citalopram, paroxetine, phenytoin, topiramate and methadone. The choice of medication should not be based on the mechanism of action but rather on consideration of other factors, including: patient comorbidities, drug side-effect profile and contraindications, drug interaction, costs and availability. If patients do not respond to or do not tolerate the drug because of side effects, another agent within the first-tier or from the second-tier with a different mechanism of action should be chosen. It may be also useful to add another first- or second-tier agent, but it is necessary to watch carefully for additive adverse effects. Some complementary pain management techniques may have value as adjuvant therapy; acupuncture has been shown to be effective in DPNP and to reduce analgesic requirement. There is no good evidence to support the use of transcutaneous electrical nerve stimulation or magnetic insoles in DPNP. There is limited evidence for the use of spinal cord stimulation, but due to the cost and the risk inherent with the procedure, its use in the clinical setting is yet to be established [6]. 3. Prevention of Complications As leg ulceration can lead to significant morbidity in diabetic patients, it is important to prevent foot ulcers in patients with DPN. Strategies to prevent leg ulcers are readily available and include [97]: education of patients to examine their feet daily; a check of the insides of shoes (to guard against chafing); the avoidance of walking barefoot; and the routine hand-testing of water temperature before bathing. Practical measures should be stressed, such as the use of a bed cradle to lift bed clothes clear of hyperaesthetic skin.

Impact of comorbid chronic pain Diabetic patients with chronic pain tend to report their health as fair or poor, and depressive symptoms are associated with significant impairment in quality of life [45]. Moreover, chronic pain is very strongly associated with a greater difficulty in exercising and the ability to follow a recommended eating plan. Comorbid chronic pain may also make self-care hard. As patients with DPNP may potentially progress to a chronic pain state, it is important to establish a good rapport with them

Pain Associated with Medical Diseases 279

in order to emphasise the positive aspects of pain management rather than to allow them to focus on the pain-related limitations. It is helpful to explain to patients the concept of pain as a warning sign versus pain as a disease, as in low back pain [6].

functioning, bodily pain, vitality, social functioning, emotional role and mental health) was shown to deteriorate significantly with increasing severity of peripheral ischaemia in Chinese patients [46]. In addition, severity of PAD and ankle-brachial index are both independent predictors of mortality [31].

Pain and Cardiovascular Diseases

The prevalence of TAO is reportedly highest in the Middle and Far East. Among patients investigated for PAD, it was found that a proportion in fact had TAO; numbers ranged from 0.5–5.6% in Western Europe, 16–66% in Korea and Japan, and up to 80% among Jews of Ashkenazi ancestry in Israel [8].

Peripheral arterial disease Background Peripheral arterial disease (PAD), also known as arteriosclerosis obliterans, is the chronic obstruction of the arteries supplying the lower extremities, and is the peripheral arterial manifestation of generalised atherosclerosis. The most widely accepted definition of PAD is a resting ankle brachial pulse index (ABPI) of 0.9 in which the ABPI is the ratio of ankle systolic pressure as measured by Doppler ultrasound and the higher of the 2 brachial systolic pressures [23]. In comparison, thromboangiitis obliterans (TAO), also called Buerger’s disease, is a segmental occlusive inflammatory condition of arteries and veins of non-atherosclerotic origin. Although it has similar clinical manifestation to PAD, TAO can also affect the upper limbs and is predominantly seen in a younger age group. Epidemiology The prevalence of PAD is approximately 20% in adults older than 55 years of age, or 27 million people in North America and Europe; the incidence increases with age. However, only half of the people experience symptoms from PAD and about onefifth of those with PAD have typical symptoms of intermittent claudication, rest pain, ulceration and gangrene [34]. Approximately 5–10% of individuals with asymptomatic PAD develop symptoms over 5 years. A similar finding in Hong Kong showed patients with PAD had a mean age of 72 years when first presenting with symptoms, with a male to female ratio of 1:1.6 [18]. Furthermore, a high proportion of patients were found with DM as a comorbidity. Femoro-popliteal artery occlusive disease contributed to the majority of PAD cases (47%). Peripheral artery disease is one of the major causes of loss of work, disability and life changes in the United States [28]. The quality of life as measured by the Medical Outcome Short Form-36 (physical

Pathophysiology The pathophysiology of PAD has been reviewed and there is evidence to suggest that Virchow’s triad: abnormal blood flow, hypercoagulability of the blood and abnormal vessel wall, is applicable in PAD [51]. Atherosclerosis is thought to be the most common culprit in PAD and is a systemic inflammatory response where cholesterol-laden plaque builds up in the artery and eventually blocks the lumen, contributing to symptomatic obstruction in the peripheral artery [28]. Risk factors that are contributory to PAD include: diabetes (or glucose intolerance), smoking, hyperlipidaemia, raised fibrinogen concentration and hyperhomocysteinaemia. The underlying mechanism for TAO remains unknown, but it is strongly associated with tobacco smoking; an immune-mediated endarteritis mechanism has also been implicated [8]. The pain mechanism due to ischaemia in PAD remains undetermined and suggested mechanisms have included [65]: putative nociceptive fibres mediate ischaemic pain; accumulation of metabolites causes sensitization of peripheral nociceptors; involvement of “mechanical determinants” of the nociceptors during ischaemia; and a central mechanism leading to a chronic pain state. Regardless of the mechanism, the pain in PAD varies depending on the speed of onset of symptoms, the extent and anatomical location of the occlusion, and the extent of collateral formation. In addition, a neuropathic pain mechanism may also play a role, especially in patients with diabetes, which is commonly associated with PAD.

280 Simon K.C. CHAN, Alice K.Y. MAN

Classification Acute peripheral arterial events are classified as: 1. Aortic events — ruptured or acute symptomatic aortic or iliac aneurysm, or thoracic aortic dissection. 2. Acute thromboembolic events — limbs or viscera. 3. Critical limb ischaemia: lower limb intermittent claudication, rest pain, skin ulcer, gangrene. About 90% of patients with severe limb ischaemia end up with amputation. Chronic critical limb ischaemia is defined as ischaemic rest pain and ischaemic ulcers or gangrene. This section will focus on the management of intermittent claudication and critical limb ischaemia in PAD, which are common presentations to pain clinics.

Clinical Features Intermittent claudication (derived from the Latin word for “limp”) is the most common symptom and is defined as leg pain that is sufficient to cause the patient to stop, is produced by exercise and relieved by rest, and is caused by arterial occlusive disease [23]. The location of pain may indicate the site of arterial occlusion: calf pain in femoral, popliteal or tibial arterial occlusion and hip, buttock, thigh pain suggestive of aorto-iliac occlusion. The temporal relationship of pain with exercise or rest may indicate the severity of the disease. Walking distance, the pain-free distance until being forced to stop, may serve as a good indicator of the disease progress. Alternatively, exercise testing with a treadmill can provide an objective measurement of walking distance and highlight other exercise limiting conditions such as arthritis or breathlessness. The severity of PAD has been classified according to its clinical symptoms (Table 17.02). Inspection of the skin, the colour and temperature of the lower limbs and the nails, may reveal trophic changes of chronic ischaemia: thin, dry skin, loss of hair or subcutaneous fat and thickened nails. Gangrenous changes, ulcer, previous amputation and muscle atrophy may also be evident. Peripheral pulses such as the dorsalis pedis and posterior tibial artery may be absent. Motor deficits indicate advanced limb-threatening ischaemia. Sensory loss (usually secondary to DM) should be documented.

Table 17.02 Classification of PAD according to severity Fontaine classification of chronic leg ischaemia Stage I Asymptomatic Stage II Intermittent claudication Stage III Ischaemic rest pain Stage IV Ulceration or gangrene, or both

Although a number of conditions can mimic PAD (Table 17.03), a careful history and physical examination can distinguish PAD from other disorders. For example, pain arising from cauda equina compression due to spinal stenosis is made worse by walking, but the pain is also brought on by prolonged standing and is not rapidly relieved by rest. Patients with PAD for consideration of invasive intervention require imaging investigations to define the anatomy of the lesion. Angiography is used to delineate the anatomy and atherosclerotic lesions before invasive therapy. However, invasive angiography is not without risk, such as from contrast reaction, and duplex ultrasound scanning is an alternative to angiography; it is non-invasive and can delineate specific lesions for suitable endovascular treatment. Another alternative is magnetic resonance angiography, which is also non-invasive, but its cost is always an issue. Thromboangiitis obliterans, on the other hand, tends to occur between the ages of 40 and 45 years and is found predominantly in men. Blood vessels Table 17.03 Differential diagnosis of peripheral arterial disease Differential diagnosis of PAD • Venous insufficiency •

Sciatica with nerve root compression

• Spinal stenosis with cauda equina compression • Hip, thigh or buttock local pathology, such as osteoarthritis • Other arterial causes: traumatic, congenital, or neoplastic

Pain Associated with Medical Diseases 281

of both the upper and lower limbs can be affected, and more than one limb is likely to be involved with the pain typically beginning in the extremities.

Management As 5-year mortality rate of 25–30% is associated with symptomatic PAD. The goal of management, in addition to the improvement of leg symptoms, is to prevent systemic complications such as stroke and myocardial infarction from ongoing atherosclerosis. The reader is referred to the recent review on the medical treatment of PAD for details of systemic complication prevention in PAD [34]. Leg symptoms can be improved with disease modification or invasive interventions aimed at improving the blood supply to the lower limbs; at the same time, pain control is an important component in managing patients with critical limb ischaemia. 1. Disease modification (a) Smoking cessation — apart from reducing systemic complications, smoking cessation reduces claudication severity and the risk of developing rest pain in patients with intermittent claudication. In addition, total smoking cessation is essential for patients with TAO to prevent disease progression and amputation. (b) Exercise rehabilitation such as a structured exercise programme can increase initial claudication distance and maximal walking distance [81]. (c) Optimise hyperlipidaemia control — using weight reduction and a statin drug. Simvastatin 20–40mg/day has been shown to reduce the incidence of claudication and improve painfree walking distance [63]. (d) Optimise hypertension control — use of a beta blocker is no longer considered to be contraindicated in PAD [68], and angiotensin converting enzyme inhibitors may improve walking distance [60]. (e) Cilostazol — a phosphodiesterase III inhibitor with vasodilator and antiplatelet activity has been demonstrated to improve maximum walking distance and pain-free walking distance. However, it remains contraindicated in patients with PAD with coexistent cardiac failure [34]. (f ) Iloprost (a prostacyclin analogue) and prostaglandin E1 have been found to reduce pain and the amputation rate for PAD in a recent meta-analysis [21].

(g) Anti-platelet agents — aspirin, although it does not improve claudication, delays the rate of progression and reduces the need for intervention and graft failure in patients after revascularisation intervention [34]. Clopidogrel is an alternative for patients who do not tolerate aspirin. (h) Anti-coagulants — heparin, low molecular weight heparin or oral anticoagulant, provide no benefit in intermittent claudication. 2. Invasive interventions Endovascular stenting, percutaneous transluminal balloon angioplasty and open surgical bypass or endarterectomy should be considered for suitable patients to improve the blood supply to the lower limbs. The reader is referred to other literature for details in this area. 3. Pain Control Patients with critical limb ischaemia describe a history of worsening claudication and progress to nocturnal rest pain. Nocturnal rest pain, which typically occurs once the patient is asleep, is due to the reduction of systemic blood pressure thereby further reducing perfusion of the foot. Patients should be referred to a vascular surgeon for consideration of urgent revascularisation. For those who are on the waiting list for invasive interventions or not candidates for revascularisation, for example those with comorbidity or an unsuitable anatomy, symptomatic pain relief with pharmacological analgesia is required. Research in analgesia for critical limb ischaemia has been limited. Racemic ketamine was demonstrated to give a dose-dependent analgesic effect in chronic ischaemic pain from PAD, but with significant “para-perceptual/dys-cognitive” side effects [65]. Transdermal buprenorphine together with spinal ropivacaine-morphine infusion was shown to provide better analgesia compared with spinal ropivacainemorphine alone for 30 days in patients with chronic pain from PAD [10], but the technique may not be feasible for patients outside the hospital setting. The pain in critical limb ischaemia can be severe and variable, seemingly spontaneous, even with patients at rest in a constant ambient temperature, and sometimes an opioid is required [65]. Hence, a stepwise analgesic approach similar to the WHO analgesic ladder is advisable for managing this group of patients. It is necessary to remember

282 Simon K.C. CHAN, Alice K.Y. MAN

that neuropathic pain may be associated with PAD and analgesia specific for neuropathic pain should always be considered when managing these patients. The choice of pharmacological agents, however, has to be cautious, as these patients are usually elderly, have vasculopathy, are on multiple medications and have a high incidence of comorbidity. The treatment strategy should, therefore, be individualised for each patient. If pain becomes intractable or intolerable side effects develop from analgesics, interventional pain therapies such as lumbar sympathectomy and spinal cord stimulation should be considered. 4. Lumbar sympathectomy Lumbar sympathectomy can be performed with open, percutaneous or endoscopic access. A previous study shows healing of gangrenous ulcer (30%) and pain relief (70%) in patients after phenol lumbar sympathectomy [54]. Careful patient selection is important for improved outcome and an ABPI >0.3 is associated with clinical improvement (Table 17.04). Moreover, the patency of the superficial femoral artery is demonstrated to be related to the successful outcome of patients [64]. There is so far no established role for adjuvant surgical sympathectomy to improve bypass graft patency or efficacy. Common complications are temporary neuralgia and unsatisfactory pain relief. Please also refer to Chapter 27 for more details on lumbar sympathectomy. 5.

Spinal cord stimulation The effects of spinal cord stimulation (SCS) in PAD have been reviewed by Tiede et al. [86] and it was found that SCS improves exercise tolerance, amputation rate and pain. The walking distance demonstrated an impressive increment. The limb salvage rate in severe PAD patients after SCS implantation was found to be 96%. Patients with intermediate preoperative microcirculatory status demonstrated an improved amputation rate (24% vs 48%, p=0.08) with SCS in a Dutch multicentre randomized controlled trial [87]. Analgesic consumption was also significantly reduced with SCS at 1, 3 and 6 months. However, patients with gangrene and trophic lesions >3cm2 may not benefit from SCS.

The beneficial effects of SCS on PAD appears to be an alteration in blood flow to the ischaemic limb,

Table 17.04 Indications for lumbar sympathectomy [22] Indications for lumbar sympathectomy • Patients with inoperable distal arterial occlusive disease secondary to atherosclerosis or TOA • Revascularisation procedure is contraindicated in case of inadequate run-off • ABPI >0.3 • Superficial necrosis limited to digits • Absence of neuropathy • Symptom relief after diagnostic lumbar sympathectomy • Acceptable surgical risk for a retroperitoneal approach

especially the microcirculatory flow. The proposed mechanisms are: (a) inhibition of the sympathetic activity involving nicotinic transmission in the ganglia and postganglionic alpha-adrenoceptors (b) the role played by afferent fibres in the dorsal root. Significant complications of SCS in PAD patients include failure (3–4%), infection (3–5%), lead dislocation and breaks (11–36%), cerebrospinal fluid leak (1%) and meningitis (0.5%) [44]. Although the role of SCS in refractory ischaemic pain and functional improvement is promising, the cost and inherent risks remain the major limiting issues for its wide clinical application. More details of SCS can be found in Chapter 29.

Coronary artery disease Background Angina is described as substernal chest pain associated with squeezing, tightness, aching, dullness, fullness, heaviness or pressure, typically aggravated by exertion or emotional stress. Refractory angina pectoris is the term applied when patients who, despite optimal medical therapy, have both angina and objective evidence of ischaemia and are not considered candidates for revascularisation [99]. This section will focus on alternative therapies for refractory angina and give a brief discussion on non-cardiac chest pain, both

Pain Associated with Medical Diseases 283

of which are common entities presented at the pain clinic.

Pathophysiology Reduced blood supply to the myocardium because of coronary atherosclerosis, spasm, or a combination of both leads to myocardial ischaemia and usually manifests as angina pectoris. Anginal pain is primarily nociceptive and arises from the adventitia of the coronary arteries and the myocardium. This afferent impulse travels along the sympathetic nerves to the upper four thoracic sympathetic ganglia and continues to enter the T1–T6 spinal cord segments [22]. Angina serves as a warning sign to patients as the reduction in their activity will limit the severity of the ischaemic injury; and this potential preconditioning effect is “beneficial” in nature [12]. In contrast, uncontrolled ischaemic pain would have potentially devastating effects on the already compromised heart, as indicated below: 1. Activation of the sympathetic nervous system resulting in hypertension, tachycardia, increase in myocardial contraction and vascular resistance. 2. Increase in myocardial oxygen demand. 3. A coupled reduction in myocardial oxygen supply due to coronary vasoconstriction. 4. The imbalance of myocardial oxygen supply and demand further exacerbates the myocardial ischaemia, creating a viscous cycle.

Management The management of angina has been reviewed by Yang et al. [99] and includes: anti-ischaemic therapy; anti-platelet/anticoagulant therapy; risk factor modification; and revascularisation. Optimal standard therapy includes administration of a betablocker and calcium channel blocker to achieve the lowest heart rate and after-load reduction. A longacting nitrate and angiotensin-converting enzyme inhibitor are also recommended. Aggressive risk factor modification, such as smoking cessation, cholesterol-modifying agents and exercise training are essential. Symptomatic control When medical treatment is optimised and surgical treatment not an option, symptomatic relief becomes the only possible treatment. Morphine is commonly included in the management of angina, but its role in refractory angina is not

established. In our experience, a weak opioid like tramadol can be successful in symptomatic control. Other pharmacological therapies which have been shown to be effective in refractory angina include [99]: ranolazine — a fatty acid oxidation inhibitor that can reduce oxygen demand; ivabradine — a specific If ion channel inhibitor to reduce heart rate and myocardial oxygen demand without a negative inotropic effect; nicordanil — a nicotinamide ester to decrease preload and after-load by vasodilatation; L-arginine — to improve blood flow by coronary dilatation; and transdermal testosterone for men and oestrogen for women — to cause coronary dilatation. If and when patients fail to respond to pharmacological intervention and become incapacitated by their symptoms, alternative therapies can be considered. These have been classified as: non-invasive non-pharmacological (transcutaneous nerve stimulation and enhanced external counterpulsation); and invasive therapies (spinal cord stimulation and transmyocardial revascularisation) [29]. 1. Transcutaneous electrical nerve stimulation Transcutaneous electrical nerve stimulation comprises a neurostimulator unit and two electrodes. An electrode is placed in the dermatome with the highest intensity of pain and the other in the opposite dermatome. The provision of 15–50 mA pulses at a frequency of 70 Hz for 1 hour three times a day with an additional 1 to 10 minutes of therapy on an as needed basis has been studied [52]. The treatment group showed better exercise tolerance during the stress test and reduction of angina symptoms. Side effects encountered include skin irritation, breakdown at the electrode sites and paraesthesia. 2. Enhanced external counterpulsation Enhanced external counterpulsation (EECP) is classified as a class IIb indication (usefulness/efficacy is less well established) device [29]. Based on the concept of counterpulsation, it comprises three pairs of pneumatic cuffs placed around the lower extremities at the level of the calves, lower thighs and upper thighs [99]. The cuffs are sequentially inflated when triggered by a corresponding electrocardiographic signal of systole and diastole. The beneficial effect of EECP may be due to nonspecific placebo effects and haemodynamic factors

284 Simon K.C. CHAN, Alice K.Y. MAN

similar to the intra-aortic balloon pump, release of vascular endothelial growth factor and training effects of the skeletal muscle [76]. It has been shown that EECP improved angina symptoms and quality of life at 2 years follow-up [77]. 3. Spinal cord stimulation Spinal cord stimulation (SCS) is a class IIb indication device for refractory angina [29]. The device consists of an epidural lead, pulse generator and connecting wires. The epidural leads are placed at the level of C7 through T1. The proposed mechanism of action includes: (a) Stimulation of the dorsal column, thus inhibiting spinothalamic tract pain transmission (b) decrease in sympathetic tone (c) improvement in myocardial blood flow. Clinical studies have demonstrated that SCS increases the time to onset of ST-segment depression, increases exercise capacity during treadmill testing, and reduces the number of anginal attacks and use of nitroglycerin. SCS was shown to be as effective as coronary artery bypass graft for improving anginal symptoms with less procedurerelated mortality [53]. A cost utility study of SCS in refractory angina, showed an annual saving of US$8,430 and the recovery of the cost of the SCS system in 15 months, due mainly to a reduction in invasive testing [15]. Despite the fact that results of studies on SCS appear promising, the intermediate and long-term benefit is yet to be determined. 4. Transmyocardial revascularisation Transmyocardial revascularisation (TMR) improves oxygen delivery to myocardial cells using either a carbon dioxide or holmium:YAG laser to generates 25–40 artificial conduits in the subendocardium via the left thoracotomy approach. The suggested mechanisms include angiogenesis because of growth-factor release, denervation of pain fibres by laser and placebo effect. Although TMR is a class IIa indication (weight of evidence favours efficacy) device for refractory angina [29], a lack of randomised controlled trials and its invasiveness have caused its use in the clinical setting to decline. Percutaneous myocardial revascularisation is similar, but performed percutaneously. It should be noted that of all the therapies discussed above, EECP is the most widely used and is the only FDA-approved treatment for refractory angina

[99]. None of the therapies, including EECP, have been shown to improve mortality in refractory angina, but they are able to improve symptoms and quality of life.

Non-cardiac chest pain Non-cardiac chest pain (NCCP) is defined as chest pain not due to cardiac ischaemia or other major physical disorders.

Epidemiology A population-based study in Hong Kong has shown that NCCP was present in 13.9% of subjects; gastrooesophageal reflux disease (GERD) was found in 51%, while 34% consulted a physician because of chest pain [96]. Factors found to be associated with the seeking of medical attention included female gender, presence of GERD and the affect of NCCP on social life. Aetiology A number of conditions can lead to chest pain of non-cardiac origin (Table 17.05), but of these GERD is the most common. Patients experience heart burn, sometimes associated with an abnormal pH test and an endoscopy finding of oesophageal erosion [25]. Patients with “Syndrome X” have typical anginal pain with ST-depression on electrocardiogram during an exercise stress test, while subsequent angiography does not show any coronary obstruction. There may be occlusions or spasm in the microvasculature around the heart, resulting in tissue ischaemia and pain [84].

Diagnosis and management Patients presenting with chest pain should be assessed by history, physical examination and relevant investigations to exclude a cardiac or other serious origin of the chest pain, such as aortic dissection. Table 17.05

Causes of non-cardiac chest pain

• Gastro-oesophageal reflux disease • Visceral hypersensitivity • Psychological origin • Oesophageal dysmotility, altered central processing of oesophageal stimuli and autonomic dysregulation, etc.

Pain Associated with Medical Diseases 285

Once non-cardiac chest pain has been diagnosed, patients should be referred to a gastroenterologist [25]. However, symptoms such as dysphagia, odynophagia, weight loss and anorexia should alert physicians that upper endoscopy is needed to detect any mucosal abnormalities. In the absence of these alarming symptoms, an empirical trial of a double dose-proton pump inhibitor (PPI) is warranted for 2–3 months. Titration to a maintenance dose should follow if there is subsequent improvement in symptoms. Otherwise, oesphageal manometry to detect achalasia and spastic motility disorder is suggested in an effort to identify other oesophageal causes of NCCP. Nitrate and calcium channel blockers have been used in non-GERD non-cardiac chest pain. Abnormal pain perception, psychiatric disorders and pain-coping strategies should be explored in patients with NCCP. Apart from pharmacological treatment with imipramine [16] or sertraline [90], coping-strategy training has also been shown to significantly reduce pain, improve psychological symptoms like anxiety and depression, alleviate psychological distress and improve the physical disability [43, 89].

Pain and Infectious Diseases Human immunodeficiency virus disease Background The human immunodeficiency virus (HIV) is a retrovirus which infects the cells of the immune system in humans leading to a decline in the body’s defences against disease. The clinical features of HIV-infected patients correlate with the CD4+Tcell count. Patients are generally asymptomatic at CD4 count >500cells/mm3. However, when the CD4 count is 75% chance of living 1 year after diagnosis of AIDS in Australia [30]. The introduction of HAART has altered the course of HIV disease and has prolonged the life of AIDS sufferers. Nevertheless, severe illnesses are likely to emerge in these patients eventually. In addition, the prolonged life span also results in an increase in prevalence of some pain syndromes, such as HIVassociated neurocognitive impairment, in these patients, which imposes a new challenge in pain management [48].

Epidemiology It was estimated that 38.6 million (33.4–46.0 million) people worldwide were HIV positive at the end of 2005. In addition, 4.1 million become newly infected with HIV and 2.8 million die due to AIDS each year [88]. Although the prevalence (the proportion of people living with HIV) has been levelling off since the late 1990s, the number of people living with HIV has continued to rise [88], and there is disparity in the prevalence between the developed and developing world. The number of new HIV infections has declined since the mid-1980s in developed countries as a result of effective prevention strategies such as public education, blood screening and needle-exchange programmes. Estimating HIV/AIDS prevalence has become difficult in the industrialised countries since the introduction of HAART as the natural course of HIV disease has been altered. At the end of 2003, it was estimated that over 1 million people in the in United States were suffering from HIV or AIDS, with 40,000 new cases diagnosed each year [20]. In Australia at the end of 2000, there were more than 10,000 people infected with HIV and 700 new cases diagnosed each year [30]. The prevalence in developing countries, compared with the Western world, remains alarming. It was estimated that 1.5 million people were HIVpositive in China in 2003 [91], but the figure fell

286 Simon K.C. CHAN, Alice K.Y. MAN

to 650,000 in 2006, as reported by the Chinese government, a figure lower than that of the 5 million in neighbouring India [92]. In South Africa, on the other hand, AIDS is the leading cause of death with 4.7 million people HIV-positive and 20.1% of adults (aged 15–49 years) living with HIV/AIDS [30].

50% and can be due to direct HIV viral infection to the central or peripheral nervous system; secondary infection by other pathogens; immune-mediated demyelination; and neurotoxicity secondary to HAART, alcohol, nutritional deficiency and/or other drugs such as anti-mycobacterials and antineoplastics [50].

The first patient was diagnosed with AIDS in Hong Kong in 1984. It remains a relatively uncommon condition in Hong Kong with 1,215 heterosexually or homosexually infected patients reported from 1987 to 2000 [95]. Although the prevalence of HIV is low, it may signal a pre-epidemic given the presence of ongoing risk behaviours such as unprotected sex [95].

Clinical features As almost all organ systems are potential targets for HIV, various pain syndromes and their origins have been described and reviewed by O’Neill et al. [61].

Pain profile In common with cancer patients, patients with HIV/ AIDS frequently experience pain. The pain tends to be of more than one type, involves more than one location and increases in intensity as the disease progresses [40]. The prevalence of significant pain ranged from 30% in the early stage of the disease to 60–70% in institutionalised AIDS patients in a 1996 International Association for the Study of Pain (IASP) report [40]. The common sites of pain with their incidence were: rheumatologically related pain (72%), dysphagia and odynophagia (30%), oral cavity pain (10–30%), chest pain (22%), abdominal pain (10–30%), peripheral neuropathy (15–20%) and headache (10–15%) [61]. A recent survey of patients with stage 4 AIDS in South Africa, however, revealed that pain was the most common symptom with a prevalence of 98%; the top five sites of pain were lower limbs (66%), mouth (50%), head (42%), throat (40%) and chest (17%) [59]. Depression, which is usually associated with chronic pain, was also found in this group of patients; the incidence of lowered mood and a feeling of hopelessness were 70% and 30% respectively [59]. Pathophysiology The mechanism of pain in HIV/AIDS is multifactorial with diverse aetiologies. Nociceptive pain can be secondary to combinations of inflammation including autoimmune responses; infection especially opportunistic infection; and neoplasms such as lymphoma or Kaposi’s sarcoma. Neuropathic pain in HIV/AIDS patients secondary to neuropathy is common with a prevalence of up to

1. Gastrointestinal pain syndromes Pain in HIV disease can arise anywhere along the gastrointestinal tract including the oral cavity, oesophagus, anus and rectum, as well as the hepatobiliary tract and pancreas. Candida infection is the most common cause of pain in the oral cavity and oesophagus, followed by ulcers from a variety of organisms, including viruses, fungi and bacteria implicated in necrotising and ulcerating infections. Infection is also an important source of pain in the anorectal region such as is caused by perirectal abscesses, cytomegalovirus proctitis, fissure-in-ano and herpes simplex infection. Right upper quadrant pain from a hepatic or pancreatic origin can have an infectious cause or be druginduced. Cytomegalovirus, cryptosporidiosis and mycobacteria are the most common infectious agents in cholecystitis, sclerosing cholangitis, hepatitis and pancreatitis. Drug-induced hepatitis and pancreatitis is commonly found secondary to antiviral agents with an incidence of between 7– 10%. 2. Chest pain syndromes Infectious causes of chest pain include Pneumocystis pneumonia, oesophagitis, pleuritis, pericarditis and postherpetic neuralgia. Kaposi’s sarcoma and lymphoma are the common neoplastic causes of chest pain. Protease inhibitors (PIs), a main component of HAART, have been shown to have deleterious metabolic effects such as dyslipidaemia and insulin resistance in patients taking them. Patients on PIs were noted to have a higher risk of developing coronary artery disease with a relative risk range from 1.26 to 2.56; the risk increases as the duration of treatment lengthens [37]. Although it remains controversial as to whether the rate of coronary events is increased in HIV patients,

Pain Associated with Medical Diseases 287

myocardial ischaemia should be one of the differential diagnoses in HIV patients with chest pain, especially in young males on PIs [37]. 3. Headache The differential diagnosis of headache in patients with HIV includes HIV encephalitis and atypical aseptic meningitis, opportunistic infections (such as toxoplasmosis and cryptococcus), AIDS-related central nervous system neoplasm, sinusitis, tension, migraine and azidothymidine (AZT)-induced headache. More ominous causes of headache should be sought for a patient with a T-cell count of below 200 [40]. 4. Neuropathic pain syndromes A variety of neuropathies have been described in HIV/AIDS patients with mechanisms as highlighted above. However, the most frequently encountered neuropathy is symmetrical predominantly sensory painful peripheral neuropathy, known as distal sensory polyneuropathy (DSP) which occurs in about one-third of all HIV-infected patients. The most likely mechanisms of DSP are immunological dysfunction secondary to HIV, and the neurotoxic effects of antiretroviral drugs (particularly dideoxynuclosides); intra-epidermal nerve fibre density from skin biopsy was found to be a valuable marker of severity [50]. 5. Rheumatological pain syndromes Several types of painful arthritis and arthropathies have been reported with HIV/AIDS. These include non-specific arthralgia, reactive arthritis, psoriatic arthritis, HIV-associated arthritis, aseptic arthritis, with Reiter’s syndrome being the most frequently reported. Muscle pain, which is common in HIV patients, is due to myopathy and polymyositis, which may be secondary to HIV infection or antiretroviral therapy, in particular AZT.

Management Due to the progressive nature and inevitably fatal course of HIV disease, as well as the multiplicity of pain occurring concurrently and the profound effect of severe pain on quality of life during the advance stage, HIV pain is considered to be similar to cancer pain. Hence, the approach used in the management of cancer pain can also be applied to the management of AIDS-related pain. When diseasespecific therapy is not available, a pharmacological approach following the WHO analgesic ladder

using opioids and co-analgesics is the mainstay of treatment for end-stage AIDS patients. However, the altered course of HIV disease resulting from the development of HAART, and the higher prevalence of psychiatric comorbidity, such as psychosocial problems and chemical dependence, in HIV patients, means that HIV/AIDS is seen as more of a chronic disease state than a progressive terminal illness, as previously thought. Therefore, a multimodal approach using the “pyramid-plusribbon” contemporary cancer pain management is advocated as being more appropriate in AIDSrelated pain [30]. This approach emphasises the importance of disease-specific therapy, psychosocial interventions and physical modalities, in addition to the analgesic ladder (Fig. 17.1). It is particularly important in managing the AIDS pain patient, because therapies such as prophylaxis for preventing opportunistic infections may be the most appropriate palliative treatment in terminal AIDS patients. The treatment of HIV-associated neuropathy has been reviewed by Luciano et al. [50] and to date the only proven effective treatment for DSP is mainly symptomatic. Lamotrigine was shown to be effective in reducing pain in DSP but not in dideoxynucleoside-induced polyneuropathy, whereas gabapentine is effective in both. Furthermore, human recombinant nerve growth factor appears to offer promising improvement in neuropathic pain and pain sensitivity. Although it is known that antiretroviral agents, dideoxynucleoside in particular, can cause neuropathy, the enhanced viral suppression from HAART may actually improve or decrease the frequency of certain types of neuropathies in HIV/AIDS. Therefore, HAART should be considered for patients with neuropathy especially with evidence of viral replication. It is not uncommon to encounter HIV patients with a past history of substance abuse; hence, when managing these patients, it is important to distinguish between active users, individuals in methadone maintenance and those in recovery, so that pain management plans can be individualised. It is also recommended that clear goals and conditions for opioid therapy are defined: set limits, make consequences clear, use written contracts and establish a single prescriber.

288 Simon K.C. CHAN, Alice K.Y. MAN

Severe Acute Respiratory Syndrome Background Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by the SARS coronavirus which led to a global outbreak in 2003. As at 31 July 2003, there were 8,098 probable cases reported and a death toll of 774 with an overall mortality rate of 9.6% [38]. The majority of patients improved with treatment, but 20–36% required intensive care admission and 13–26% progressed to acute respiratory distress syndrome (ARDS) requiring ventilatory support. In addition to supportive therapies, SARS patients were treated with antiviral agents — ribavirin, lopinavir or ritonavir — and, if they deteriorated further, were given high-dose methylprednisolone 0.5 g daily to avoid immunopathological lung injury [38]. Post-SARS patients were followed up for 1 year and were found to have favourable pulmonary recovery comparable to post-ARDS patients. However, when compared with normal subjects, post-SARS patients were found to have a significantly lower 6-minute walk distance and impairment of health-related quality of life as measured by SF-36, which may have resulted from generalised muscle weakness and myopathy [39]. Pathophysiology The effect of pain on post-SARS patients is still unclear as the literature on this issue remains scant. However, it appears that pain is common in SARS patients, at least in the acute phase. Although fever and respiratory symptoms were the predominant clinical features, 45–61% of SARS patients had myalgia [38] and 32% had raised creatine kinase [47] on presentation. In addition, 53% of patients who had no prior joint symptoms nor predisposition to osteonecrosis developed large joint pain after SARS infection, but only 5% showed evidence of subchondral osteonecrosis on magnetic resonance imaging after recovery from SARS [33]. In a small series of 30 post-SARS patients (published in Chinese), 87% developed arthralgia [27] and there is a case report of fibromyalgia [85]. A number of mechanisms have been implicated for these musculoskeletal involvements, including critical illness polyneuropathy and/or myopathy; steroid-induced myopathy and osteonecrosis; deconditioning due to prolonged confinement;

and SARS-induced myopathy and arthralgia [33, 39].

Management The pain management for post-SARS patients poses a number of challenges: unknown mechanism of pain in SARS, uncertain natural course of SARS recovery, potential litigation and high prevalence of mood and psychological disturbances [19]. Treatment is mainly supportive and pain should be managed with a multidisciplinary approach using multimodal analgesia, physical therapy and psychotherapy. It is important to exclude osteonecrosis and to consult an orthopaedic surgeon if indicated clinically, especially in patients who have received more than the equivalent of 3 g prednisolone for SARS treatment [33].

Pain and Haematological Disorders Haemophilia Background and pathophysiology Haemophilia is a sex-linked genetic coagulation disorder due to qualitative or quantitative defects of clotting factors. Although all clotting factors can be affected, defect in Factor VIII (haemophilia A) and Factor IX (haemophilia B) are the most common inherited coagulation disorders. The severity of haemophilia depends on the plasma concentration of clotting factor and is graded as severe if the concentration is less than 1%. The major complication of haemophilia is intraarticular bleeding to the large joints leading to repeated haemarthrosis, chronic synovitis, epiphyseal overgrowth, destruction of cartilage and eventually joint deformity in the adolescent. The pain and joint deformity have a profound effect on the function and quality of life for haemophilia sufferers [35]. Management The disease process can be modified with prophylactic factor replacement to maintain plasma factor level >1% between 1 and 3 years of age to prevent joint destruction [9]. Recombinant factor is now preferred to avoid disease transmission of HIV or hepatitis viruses. Corticosteroids have been used to decrease synovium in chronic synovitis with good but temporary results. Non-

Pain Associated with Medical Diseases 289

steroidal anti-inflammatory drugs have a limited role in this situation due to the associated risk of bleeding. However, celecoxib, a cyclo-oxygenase-2 inhibitor, has been shown to be safe and effective in treating chronic synovitis and joint pain in haemophilia [70]. In situations where medical prophylaxis is not possible, such as unavailability of factor product or development of inhibitors to transfused product, open or arthroscopic surgical synovectomy can effectively retard the pathological process of haemophilic arthropathy. More recently, intra-articular injection of chemical or radioisotope sclerosing agent has been used as the alternative for surgical synovectomy and found to have short-term effect [35]. Total joint replacement may be the ultimate procedure for haemophilic arthropathy and can bring considerable improvement in joint movement and pain relief. It is important to stress that supportive physical therapy is a lifelong need and should always be part of an integral management plan for this group of patients.

Most sickle cell disease patients with acute painful episodes have been under-treated. Their minority ethnic origin and lower socioeconomic class; recurrent multiple presentations to hospital with pain; and fear of opioid dependence all imposed a barrier to the proper management of these patients. This situation prompted the publication of guidelines to assist the management of pain associated with this disease [71]: 1. Arrangement for fast-track hospital admission and assessment. 2. Aggressive and early pain control according to the WHO analgesic ladder. 3. Morphine is the first choice of opioid analgesic and patient-controlled analgesia is recommended if facilities are available. 4. Non-pharmacological pain management such as psychological and physical approaches are beneficial. 5. Other general measures, such as rehydration, oxygen supplement, antibiotics and blood transfusion if indicated.

Sickle cell disease Background Sickle cell disease is an inherited haemoglobin disorder. Chronic haemolytic anaemia occurs in homozygous inheritance of haemoglobin S characterised by the sickle-shaped red blood cells causing vaso-occlusion and infarction. Throughout their lives the homozygotes are affected by recurrent painful episodes which are highly variable in frequency and severity among patients. Advances have been made recently in the understanding and treatment that significantly improve outcomes in sickle cell disease. Guidelines and recommendations are readily available to assist physicians in managing these patients [55, 71]. Management Interventions recommended to modify the disease processes from childhood to avoid permanent damages include [55]: prophylactic antibiotics with daily penicillin V potassium from 2 months of age until age 5 years; childhood immunisation with 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide pneumococcal vaccine for children less than 2 years and older than 2 years respectively; hydroxyurea, which can increase haemoglobin F levels and improve red cells deformability, should be considered for those who have frequent severe painful episodes.

Pain and Pancreatic Disorders Acute pancreatitis Background Acute pancreatitis is an acute inflammatory disorder of the pancreas caused by an intracellular activation of pancreatic digestive enzymes. It represents a spectrum of disease ranging from a mild, self-limiting course to a rapidly progressive, potentially fatal illness. The destruction of pancreatic parenchyma induces a systemic activation of coagulation, kinin, complement and fibrinolytic cascades with liberation of cytokines and reactive oxygen metabolites which, in severe cases, can lead to shock, acute renal failure and the acute respiratory distress syndrome. Nevertheless, in 70–80% of patients with acute pancreatitis, the disease is mild and responds to supportive measures alone. Management The principle of management of acute pancreatitis includes: monitoring of vital signs, fluid replacement, correction of electrolytes disturbance, nutritional support, prevention of local and systemic complications, and pain relief.

290 Simon K.C. CHAN, Alice K.Y. MAN

As acute pancreatitis is accompanied by persistent severe pain which may have potential adverse effect, analgesia is considered to be crucial in managing patients with acute pancreatitis and buprenorphine is recommended [80]. However, when potent opioid is required, there is always concern for the effect of opioid on the pressure of the sphincter of Oddi. In a recent review by Thompson [82], it was noted that all opioids including pethidine increase the pressure of the sphincter of Oddi, but there is no evidence to indicate that morphine is contraindicated in acute pancreatitis. Hence, morphine is considered to be more appropriate than pethidine as it provides a longer duration of analgesia without the risk of norpethidine-induced seizure [82]. Although various invasive pain relief procedures have been described, they are rarely used in the clinical setting because of potential cardiovascular instability and sepsis.

Chronic pancreatitis Background Chronic pancreatitis (CP) is a progressive inflammatory process of the pancreas leading eventually over years to fibrotic destruction of the pancreas resulting in exocrine and endocrine insufficiency. Although other symptoms may also occur, pain is a prominent symptom and at least 85% of patients with CP will develop pain at some time during the course of the disease; as there is no definitive treatment to counteract the inflammatory process[4], pain control becomes an important element in the management of CP.

Aetiology and pathophysiology The incidence of CP was estimated to be between 7.7 and 8.2 per 100,000 per year with an overall prevalence of 27.4 cases per 100,000 in a population [49, 73]. The commonest cause of CP is alcoholism (70–80%), followed by idiopathic CP (20%). Some other rare causes include genetic mutation, hyperparathyroidism, trauma or autoimmunity. It was previously thought that acute pancreatitis and CP were two separate disease entities with different pathophysiological mechanisms, but there is now increasing evidence that alcoholic acute pancreatitis and CP are different stages of the same disease entity (sentinel acute pancreatitis event hypothesis) [73]. Alcoholic CP is a slow process evolving in two

stages: early-stage CP with recurrent episodes of acute pancreatitis; and late-stage CP with exocrine and endocrine insufficiency and calcification of pancreas. The progression rate to late-stage CP due to alcoholism is variable with an average of 5 years. Whereas hereditary and idiopathic CP have a significantly prolonged early-stage and a marked delay in onset of late-stage [3]. Although acute and late-stage CP are easily diagnosed, it is always difficult to diagnose the onset, i.e. early-stage CP. The pathogenesis of CP is still unknown and several hypothetical concepts have been proposed to explain the early and late pathophysiological changes in CP including [73]: 1. Intraductal obstruction hypothesis — chronic alcohol ingestion, by unknown mechanism, causes reduced bicarbonate concentration and volume of pancreatic secretion leading to precipitation of protein and calcium salts; and the resultant ductal obstruction. Ductal hypertension plays an important role in pancreatic inflammation and finally fibrosis. 2. Necrosis-fibrosis hypothesis — repeated episodes of acute pancreatitis lead to areas of focal necrosis and healing which eventually end up with pancreatic fibrosis. CP represents a late stage of relapsing acute pancreatitis. 3. Toxic-metabolic hypothesis — alcohol or other toxins change the intracellular lipid metabolism leading to fatty degeneration of pancreatic acinar cells. 4. Oxidative stress hypothesis — oxygen free radical formation from alcohol/toxin exposure damages the pancreatic acinar cells with resultant CP. 5. Sentinel acute pancreatitis event hypothesis — chronic alcohol exposure leads to elevation of stress cytokines, oxidative stress and mitochondrial damage. Pancreatic autodigestion during an episode of acute pancreatitis leads to the release of cytokines, recruitment of neutrophils, monocytes and lymphocytes into the pancreas and activation of pancreatic stellate cells. With recurrent injury to the pancreas, there is continued release of cytokines leading to the eventual pancreatic fibrosis. Although different aetiologies lead to different courses of the disease and different pain profiles (see below), continuous damage to pancreatic acini and lobular destruction result in progressive

Pain Associated with Medical Diseases 291

loss of pancreatic exocrine tissue irrespective of the aetiology. The islets of Langerhans are not initially involved in the inflammatory process; however, gradual loss of endocrine tissue occurs eventually. The neuroanatomy for the pain transmission in CP has been reviewed by Bradley et al. [14] and splanchnic nerves are thought to carry most of the afferent fibres from the pancreas. In addition, afferent pain fibres from the pancreas are also found in some of the somatic nerve pathways and other mixed nerves, such as the vagus. Different mechanisms of pain have been proposed: ductal hypertension leads to increased pancreatic parenchymal pressure and produces pain by direct pressure on sensory nerves; increased pancreatic pressure results in a “compartment syndrome”, producing chronic ischaemia and parenchymal acidosis; and direct contact of the sensory nerves with parenchymal neural irritants.

Clinical features and pain profile The early-stage CP is characterised by recurrent painful attacks of acute pancreatitis. The earlystage may last for several years and is followed by the late-stage CP with development of chronic pain, pancreatic calcifications and pancreatic insufficiency. Abdominal pain is typically worsened after a meal, which limits the food intake and contributes to weight loss and malnutrition. Two types of pain in CP have been described: A-type pain — short relapsing pain episodes which last for 2 to 10 days and separated by long pain-free periods of months (or years); and B-type pain — prolonged periods of either persistent (daily) pain or clusters of recurrent severe pain exacerbations for at least 2 months which require repeated hospitalisation [3]. Type-A pain links recurrent attacks of acute pancreatitis with the initiation of alcoholic CP, whereas persistent severe B-type pain is usually associated with local complications, such as pseudocysts or obstructive cholestasis. The course of pain in CP remains unpredictable and highly variable, but spontaneous partial or complete pain relief in late-stage CP is common and noted in 50–80% of patients and is closely related to the development of marked exocrine insufficiency. The interval between the onset and occurrence of persistent exocrine insufficiency and pancreatic calcification is about 5 years in alcoholic CP, but is less well defined in nonalcoholic CP.

Management There are three aspects to the management of CP: abstinence from alcohol and smoking; supportive therapy for exocrine and endocrine insufficiency; and pain control. Alcohol and smoking are noted to be independent risk factors for the developments of CP, and avoidance of the precipitating factors have been shown to reduce the pain as well as to slow the progression of the disease [66]. Details of supportive therapy for exocrine and endocrine insufficiency are beyond the scope of this book and the reader is referred to other medical textbooks. A number of measures have been proposed to reduce pancreatic enzyme secretion and thereby reduce pain. These measures include pancreatic enzyme supplementation, elevation of duodenal pH with cimetidine or proton pump inhibitors; and somatostatin analog octreotide. Although conflicting results have been found with these measures, they are still widely used in the clinical setting [66]. When avoidance of precipitating factors and other general measures fail to provide pain relief, a pharmacological approach using the WHO analgesic ladder is recommended [58]. It should be noted that although all opioids will increase the sphincter of Oddi pressure, it is thought that the benefits of morphine may outweigh its risk in treating pancreatitis [82]. Nevertheless, caution is advised when using potent opioids in CP patients, and a partial agonist or agonist/antagonist may be considered [66]. When the pain becomes intractable or in the setting of increasing pain (type-B pain), radiological examination of the pancreatic morphology is recommended and endoscopic intervention, denervation procedures or surgical therapy should be considered. Endoscopic interventions such as stent placement, stone extraction, stricture dilatation and pancreatic sphincterotomy were found to be beneficial in patients with large duct and ductal hypertension [66]. Variable results of neurolytic coeliac plexus block either by endoscopic ultrasound or transcutaneous approaches have been observed in CP patients; the mean pain-free period was only 2 months, even for successful blocks, and the procedure is therefore not recommended for routine practice [66]. Various open surgical denervation procedures have been described. These include bilateral thoracoscopic splanchnicectomy

292 Simon K.C. CHAN, Alice K.Y. MAN

after patient selection with differential epidural analgesia, which appears to be promising [14]. Operative treatments, such as surgical resection or drainage and longitudinal pancreatico-jejunostomy, have been advocated for the management of CP and have been found to be superior to endoscopic intervention [66]. It should be reminded that operative therapy in CP is effective in reducing pain, but does not retard the disease process and hence should not be undertaken for the purpose of improving endocrine or exocrine function.

Pancreatic cancer Background Pancreatic cancer is the fifth commonest cause of cancer-related deaths in Australia [83]. The majority of patients have metastasis or advanced local disease at the time of presentation and are unresectable. Therefore, palliative management of symptoms becomes the prime concern. The three main symptoms in pancreatic cancer are pain, weight loss and jaundice; but pain is often the most feared by patients. Moreover, the presence of pain has been shown to have an inverse correlation with survival [5]. Management The general principle in cancer pain management has been discussed in Chapter 9, and pain management relevant to pancreatic cancer is highlighted in this section. A recent systematic review on neurolytic coeliac plexus block for pain control in pancreatic cancer has found that the intervention improves the quality of analgesia and reduces the opioid requirement, but has no effect on survival [98]. In addition, bilateral thoracoscopic splanchnicectomy has been shown to significantly reduce the mean pain score from 7.4 to 0.6, and the effect persisted for 3 months at the time of follow-up in unresectable pancreatic cancer [67]. Therefore, depending on the availability of expertise and facility, it is appropriate to consider neuroablation procedures for those patients who continue to suffer from severe pain despite pharmacological analgesia.

Visceral Pain Visceral pain may arise from any internal organs within the thorax, abdomen or pelvis. Viscera are innervated by both extrinsic and intrinsic nervous

systems but they interact in a poorly understood manner. Visceral sensory neurons are responsible for detecting chemical, thermal and mechanical stimuli, and can be sensitised by local ischaemia, hypoxia and the consequent release of inflammatory mediators after local inflammation or tissue injury [17]. Viscero-visceral convergence occurs when visceral afferents from the different internal organs, such as the urinary bladder, uterus and vagina, converge on the same dorsal horn neurons, resulting in augmentation of pain symptoms. In addition, most visceral afferents also converge on dorsal horn neurons innervated by somatic afferent neurons, causing viscero-somatic convergence. This convergence of inputs is thought to be responsible for the vague, poorly defined pain pattern and referred pain in visceral pain. Pain arising from viscera can be due to an underlying pathological process, such as myocardial ischaemia; or is deemed “functional” when no identifiable cause is found, for example irritable bowel syndrome. Treatment of organic visceral pain should be directed to the underlying cause, whereas a multidisciplinary approach is needed to manage visceral pain that is functional in origin. A detailed description of all visceral pain is beyond the scope of this book and only functional pain arising from the gastrointestinal tract and pelvic organs will be discussed.

Functional gastrointestinal disorders Background A variety of functional gastrointestinal disorders (FGIDs) with variable symptoms including pain, diarrhoea, constipation, bloating, nausea and vomiting have been described, but the recent Rome III Classification System of FGID, which is based on symptomatology and age group, is gaining popularity [24]. For example, irritable bowel syndrome has been defined as recurrent abdominal pain or discomfort occurring at least 3 days a month in the previous 3 months with an associated change in bowel habit [24]. The incidence of irritable bowel syndrome is around 10–15% of the general population in the developed world [72, 93]. Although no aetiology has been identified, a number of contributory factors have been implicated in relation to the pathophysiology of FGIDs [24]: genetic predisposition; early family

Pain Associated with Medical Diseases 293

environment; psychosocial factors; abnormal gut motility; activated mucosal inflammatory cells; altered bacterial flora; and interactions of brain-gut via the central nervous system and enteric nervous system.

Management Once serious pathological processes, such as neoplastic, inflammatory and infectious disorders, have been excluded and a diagnosis of FGID is made, a number of therapeutic options, which depend on severity of symptoms, are available [24]. 1. Education — emphasising that both physiological and psychological factors interact to produce symptoms. 2. Reassurance. 3. Dietary and/or medication modification. 4. Symptom monitoring — to identify precipitating factor, if any. 5. Pharmacotherapy for symptomatic relief, such as laxativess or antispasmodics. 6. Psychological treatment. 7. Antidepressants — there is moderate evidence (NNT 4.2) to support the use of tricyclic antidepressant in irritable bowel syndrome probably due to their anticholinergic effect and mechanism relating to pain modulation in the central nervous system. Furthermore, serotonin-noradrenergic reuptake inhibitors, such as duloxetine, were recently found to have a role in controlling pain in FGIDs, probably via a central analgesic action as well as relief of associated symptoms of depression. Regardless of treatment approaches, the key for successful and satisfactory management is the establishment of the physician-patient relationship. Patients with severe symptoms who become disabled or have severe function impairment should be referred to a pain centre which can provide a multidisciplinary approach for rehabilitation.

Chronic pelvic pain Background Chronic pelvic pain may have an apparent gynaecological origin but no definite lesion or cause on examination [56]. It is also defined as persistent pain of at least 6 months’ duration felt in the lower

abdomen or pelvis and not associated exclusively with menstruation, pregnancy or intercourse [57]. The prevalence of chronic pelvic pain is 25.4% in women aged between 18 and 50 years, about half of whom will have chronic pelvic pain of no known aetiology [32].

Management A multidisciplinary approach is recommended in the management of patients with chronic pelvic pain to reduce pain and improve daily activity [78]. Treatment modalities available specific to chronic pelvic pain include: 1. Pharmacotherapy — simple analgesics (e.g. paracetamol) and non-steroidal antiinflammatory drugs should be prescribed for all patients with chronic pelvic pain. Adjunct analgesics like the tricyclic antidepressants are considered second-line treatment for chronic pelvic pain. Hormonal treatments are indicated if pelvic pain is strongly cyclical with gonadotrophin-releasing hormone analogues, which induce a reversible, menopause-like state of hypogonadotropic hypogonadism [42]. 2. Surgery — improvement in pain at 1 year in 60% of patients following hysterectomy was reported in a series of 300 patients with chronic pelvic pain [36]. Adhesiolysis is not associated with improved outcome unless adhesions are very severe, but the use of diagnostic ultrasound or laparoscopy to rule out serious conditions and provide reassurance in patients with persistent pelvic visceral pain is recommended in a systematic review [78]. More recently, however, a blinded randomised controlled study has found no difference in chronic pelvic pain reduction between laparoscopic adhesiolysis and diagnostic laparoscopy alone [79]. 3. Neurostimulation and neurolytic intervention — the experience of neurostimulation and neurolysis in managing chronic pelvic pain is limited to anecdotal reports and case series. There is inadequate evidence supporting the role of laparoscopic uterosacral nerve ablation [78]. In a case series of patients with deep pelvic, retropubic pain, vulvodynia, dyspareunia and rectal pains, spinal cord stimulation has been reported to provide satisfactory pain relief [41].

294 Simon K.C. CHAN, Alice K.Y. MAN

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29.

30.

Report and recommendations of the San Antonio conference on diabetic neuropathy. Consensus statement. Diabetes 1988;37(7):1000–4. DCCT Research Group. Effect of intensive diabetes treatment on nerve conduction in the Diabetes Control and Complications Trial. Ann Neurol 1995;38(6):869–80. Ammann RW. Diagnosis and management of chronic pancreatitis: Current knowledge. Swiss Med Wkly 2006;136(1112):166–74. Andren-Sandberg A, Hoem D, Gislason H. Pain management in chronic pancreatitis. Eur J Gastroenterol Hepatol 2002;14(9):957–70. Andren-Sandberg A, Viste A, Horn A, et al. Pain management of pancreatic cancer. Ann Oncol 1999;10(Suppl 4):265– 8. Argoff CE, Backonja MM, Belgrade MJ, et al. Consensus guidelines: Treatment planning and options. Diabetic peripheral neuropathic pain. Mayo Clin Proc 2006;81(Suppl 4):S12–25. Argoff CE, Cole BE, Fishbain DA,et al. Diabetic peripheral neuropathic pain: Clinical and quality-of-life issues. Mayo Clin Proc 2006;81(Suppl 4):S3–11. Arkkila PE. Thromboangiitis obliterans (Buerger’s disease). Orphanet J Rare Dis 2006;1:14. Astermark J, Petrini P, Tengborn L, et al. Primary prophylaxis in severe haemophilia should be started at an early age but can be individualised. Br J Haematol 1999;105(4):1109–13. Aurilio B, Pace MC, Passavanti MB. Transdermal buprenorphine combined with spinal morphine and naropine for pain relief in chronic peripheral vasculopathy. Minerva Anestesiol 2005;71(7-8):445–9. Bansal V, Kalita J, Misra UK. Diabetic neuropathy. Postgrad Med J 2006;82(964):95–100. Bolli R, Abdel-Latif A. No pain, no gain: The useful function of angina. Circulation 2005;112(23):3541–3. Boulton AJ, Gries FA, Jervell JA. Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy. Diabet Med 1998;15(6):508–14. Bradley EL 3rd, Bem J. Nerve blocks and neuroablative surgery for chronic pancreatitis. World J Surg 2003;27(11):1241– 8. Buchser E, Durrer A, Albrecht E. Spinal cord stimulation for the management of refractory angina pectoris. J Pain Symptom Manage 2006;31(Suppl 4):S36–42. Cannon RO 3rd, Quyyumi AA, Mincemoyer R, et al. Imipramine in patients with chest pain despite normal coronary angiograms. N Engl J Med 1994;330(20):1411–7. Cervero F, Laird JM. Understanding the signaling and transmission of visceral nociceptive events. J Neurobiol 2004;61(1):45–54. Cheng SW, Ting AC, Lau H, et al. Epidemiology of atherosclerotic peripheral arterial occlusive disease in Hong Kong. World J Surg 1999;23(2):202–6. Chua SE, Cheung V, McAlonan GM, et al. Stress and psychological impact on SARS patients during the outbreak. Can J Psychiatry 2004;49(6):385–90. Control CfD. Basic statistics from the Division HIV/AIDS Prevention. Vol. 2006, 2003. Creutzig A, Lehmacher W, Elze M. Meta-analysis of randomised controlled prostaglandin E1 studies in peripheral arterial occlusive disease stages III and IV. Vasa 2004;33(3):137–44. Deer TR, Raso LJ. Spinal cord stimulation for refractory angina pectoris and peripheral vascular disease. Pain Physician 2006;9(4):347–52. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg 2000;31(1 Pt 2):S1–S296. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006;130(5):1377– 90. Fass R, Dickman R. Non-cardiac chest pain: An update. Neurogastroenterol Motil 2006;18(6):408–17. Fields HL, Martin JB. Pain: Pathophysiology and management. In Kasper DL, Fauci AS, Longo DL, et al., eds. Harrison’s Principles of Internal Medicine, Vol. 1. McGraw-Hill, 2005:71–5. Gao HS, Wang SX, Chen LM, et al. [Analysis of relation between the usage of corticosteroid in treatment and arthralgia as a sequela of SARS patients]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2004;16(5):277–80. Garcia LA. Epidemiology and pathophysiology of lower extremity peripheral arterial disease. J Endovasc Ther 2006;13 (Suppl 2):II3–9. Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guidelines update for the management of patients with chronic stable angina—summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). Circulation 2003;107(1):149–58. Glare PA. Pain in patients with HIV infection: Issues for the new millennium. Eur J Pain 2001;(5 Suppl A):43–8.

Pain Associated with Medical Diseases 295 31. Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: Morbidity and mortality implications. Circulation 2006;114(7):688–99. 32. Grace VM, Zondervan KT. Chronic pelvic pain in New Zealand: Prevalence, pain severity, diagnoses and use of the health services. Aust N Z J Public Health 2004;28(4):369–75. 33. Griffith JF, Antonio GE, Kumta SM, et al. Osteonecrosis of hip and knee in patients with severe acute respiratory syndrome treated with steroids. Radiology 2005;235(1):168–75. 34. Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA 2006;295(5):547– 53. 35. Hilgartner MW. Current treatment of hemophilic arthropathy. Curr Opin Pediatr 2002;14(1):46–9. 36. Hillis SD, Marchbanks PA, Peterson HB. The effectiveness of hysterectomy for chronic pelvic pain. Obstet Gynecol 1995;86(6):941–5. 37. Hsue PY, Waters DD. What a cardiologist needs to know about patients with human immunodeficiency virus infection. Circulation 2005;112(25):3947–57. 38. Hui DS, Chan MC, Wu AK, et al. Severe acute respiratory syndrome (SARS): Epidemiology and clinical features. Postgrad Med J 2004;80(945):373–81. 39. Hui DS, Wong KT, Ko FW, et al. The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors. Chest 2005;128(4):2247–61. 40. IASP. Pain in AIDS: A Call for Action. International Association for the Study of Pain, 1996. 41. Kapural L, Narouze SN, Janicki TI, et al. Spinal cord stimulation is an effective treatment for the chronic intractable visceral pelvic pain. Pain Med 2006;7(5):440–3. 42. Kennedy S, Bergqvist A, Chapron C, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005;20(10):2698–704. 43. Klimes I, Mayou RA, Pearce MJ, et al. Psychological treatment for atypical non-cardiac chest pain: A controlled evaluation. Psychol Med 1990;20(3):605–11. 44. Klomp HM, Spincemaille GH, Steyerberg EW, et al. Spinal-cord stimulation in critical limb ischaemia: A randomised trial. ESES Study Group. Lancet 1999;353(9158):1040–4. 45. Krein SL, Heisler M, Piette JD, et al. The effect of chronic pain on diabetes patients’ self-management. Diabetes Care 2005;28(1):65–70. 46. Lau H. Quality of life analysis in Chinese patients with peripheral vascular disease. Chin Med J 2001;114(9):88–103. 47. Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003;348(20):1986–94. 48. Letendre S, Ellis RJ. Neurologic complications of HIV disease and their treatments. Top HIV Med 2006;14(1):21–6. 49. Levy P, Barthet M, Mollard BR, et al. Estimation of the prevalence and incidence of chronic pancreatitis and its complications. Gastroenterol Clin Biol 2006;30(6-7):838–44. 50. Luciano CA, Pardo CA, McArthur JC. Recent developments in the HIV neuropathies. Curr Opin Neurol 2003;16(3):403– 9. 51. Makin A, Silverman SH, Lip GY. Peripheral vascular disease and Virchow’s triad for thrombogenesis. Q J Med 2002;95(4):199–210. 52. Mannheimer C, Carlsson CA, Emanuelsson H, et al. The effects of transcutaneous electrical nerve stimulation in patients with severe angina pectoris. Circulation 1985;71(2):308–16. 53. Mannheimer C, Eliasson T, Augustinsson LE, et al. Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: The ESBY study. Circulation 1998;97(12):1157–63. 54. Mashiah A, Soroker D, Pasik S, et al. Phenol lumbar sympathetic block in diabetic lower limb ischemia. J Cardiovasc Risk 1995;2(5):467–9. 55. Mehta SR, Afenyi-Annan A, Byrns PJ, et al. Opportunities to improve outcomes in sickle cell disease. Am Fam Physician 2006;74(2):303–10. 56. Merskey H, Bogduk N. Classification of Chronic Pain, 2nd edn. IASP, 1994. 57. Moore J, Kennedy S. Causes of chronic pelvic pain. Bailliere’s Best Pract Res Clin Obstet Gynaecol 2000;14(3):389– 402. 58. Mossner J, Keim V, Niederau C, et al. [Guidelines for therapy of chronic pancreatitis. Consensus Conference of the German Society of Digestive and Metabolic Diseases. Halle 21–23 November 1996]. Z Gastroenterol 1998;36(5):359– 67. 59. Norval DA. Symptoms and sites of pain experienced by AIDS patients. S Afr Med J 2004;94(6):450–4. 60. Novo S, Abrignani MG, Pavone G, et al. Effects of captopril and ticlopidine, alone or in combination, in hypertensive patients with intermittent claudication. Int Angiol 1996;15(2):169–74. 61. O’Neill WM, Sherrard JS. Pain in human immunodeficiency virus disease: A review. Pain 1993;54(1):3–14. 62. Palella FJ Jr, Baker RK, Moorman AC, et al. Mortality in the highly active antiretroviral therapy era: Changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr 2006;43(1):27–34.

296 Simon K.C. CHAN, Alice K.Y. MAN 63. Pedersen TR, Kjekshus J, Pyorala K, et al. Effect of simvastatin on ischemic signs and symptoms in the Scandinavian simvastatin survival study (4S). Am J Cardiol 1998;81(3):333–5. 64. Perez-Burkhardt JL, Gonzalez-Fajardo JA, Martin JF, et al. Lumbar sympathectomy as an isolated technique for the treatment of lower limbs chronic ischemia. J Cardiovasc Surg (Torino) 1999;40(1):7–13. 65. Persson J, Hasselstrom J, Wiklund B, et al. The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans. Acta Anaesthesiol Scand 1998;42(7):750–8. 66. Pfutzer RH, Schneider A. Treatment of alcoholic pancreatitis. Dig Dis 2005;23(3-4):241–6. 67. Pietrabissa A, Vistoli F, Carobbi A, et al. Thoracoscopic splanchnicectomy for pain relief in unresectable pancreatic cancer. Arch Surg 2000;135(3):332–5. 68. Radack K, Deck C. Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials. Arch Intern Med 1991;151(9):1769–76. 69. Rathur HM, Boulton AJ. Recent advances in the diagnosis and management of diabetic neuropathy. J Bone Joint Surg Br 2005; 87(12):1605–10. 70. Rattray B, Nugent DJ, Young G. Celecoxib in the treatment of haemophilic synovitis, target joints, and pain in adults and children with haemophilia. Haemophilia 2006;12(5):514–7. 71. Rees DC, Olujohungbe AD, Parker NE, et al. Guidelines for the management of the acute painful crisis in sickle cell disease. Br J Haematol 2003;120(5):744–52. 72. Saito YA, Schoenfeld P, Locke GR 3rd. The epidemiology of irritable bowel syndrome in North America: A systematic review. Am J Gastroenterol 2002;97(8):1910–5. 73. Schneider A, Singer MV. Alcoholic pancreatitis. Dig Dis 2005;23(3-4):222–31. 74. Sima AA, Calvani M, Mehra M, et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: An analysis of two randomized placebo-controlled trials. Diabetes Care 2005;28(1):89–94. 75. Sima AA, Sugimoto K. Experimental diabetic neuropathy: an update. Diabetologia 1999;42(7):773–88. 76. Sinvhal RM, Gowda RM, Khan IA. Enhanced external counterpulsation for refractory angina pectoris. Heart 2003;89(8):830–3. 77. Soran O, Kennard ED, Kfoury AG, et al. Two-year clinical outcomes after enhanced external counterpulsation (EECP) therapy in patients with refractory angina pectoris and left ventricular dysfunction (report from The International EECP Patient Registry). Am J Cardiol 2006;97(1):17–20. 78. Stones RW, Mountfield J. Interventions for treating chronic pelvic pain in women. Cochrane Database Syst Rev 2000;(4): CD000387. 79. Swank DJ, Swank-Bordewijk SC, Hop WC, et al. Laparoscopic adhesiolysis in patients with chronic abdominal pain: A blinded randomised controlled multi-centre trial. Lancet 2003; 361(9365):1247–51. 80. Takeda K, Takada T, Kawarada Y, et al. JPN Guidelines for the management of acute pancreatitis: Medical management of acute pancreatitis. J Hepatobiliary Pancreat Surg 2006;13(1):42–7. 81. Tan KH, De Cossart L, Edwards PR. Exercise training and peripheral vascular disease. Br J Surg 2000;87(5):553–62. 82. Thompson DR. Narcotic analgesic effects on the sphincter of Oddi: A review of the data and therapeutic implications in treating pancreatitis. Am J Gastroenterol 2001;96(4):1266–72. 83. Thomson BN, Banting SW, Gibbs P. Pancreatic cancer — current management. Aust Fam Physician 2006;35(4):212– 7. 84. Thurston RC, Keefe FJ, Bradley L, et al. Chest pain in the absence of coronary artery disease: A biopsychosocial perspective. Pain 2001;93(2):95–100. 85. Tian XP, Zeng XF, Xu WB. Fibromyalgia after severe acute respiratory syndrome: a case report. Chin Med J (Engl) 2006;119(10):875–7. 86. Tiede JM, Huntoon MA. Review of spinal cord stimulation in peripheral arterial disease. Neuromodulation 2004;7(3):168–75. 87. Ubbink D, Spincemaille G, Prins M. Microcirculatory investigations to determine the effect of spinal cord stimulation for critical leg ischemia: The Dutch multicenter randomized controlled trial. J Vasc Surg 1999(30):326–44. 88. UNAIDS. Report on the global AIDS epidemic 2006. Joint United Nations Programme on HIV/AIDS, 2006. 89. van Peski-Oosterbaan AS, Spinhoven P, van Rood Y, et al. Cognitive-behavioral therapy for noncardiac chest pain: A randomized trial. Am J Med 1999;106(4):424–9. 90. Varia I, Logue E, O’Connor C, et al. Randomized trial of sertraline in patients with unexplained chest pain of noncardiac origin. Am Heart J 2000;140(3):367–72. 91. Watts J. China faces up to HIV/AIDS epidemic. World AIDS day is marked by launch of huge public-awareness campaign. Lancet 2003;362(9400):1983. 92. Watts J. AIDS in China: New legislation, old doubts. Lancet 2006;367(9513):803–4. 93. Wilson S, Roberts L, Roalfe A, et al. Prevalence of irritable bowel syndrome: A community survey. Br J Gen Pract 2004;54(504):495–502.

Pain Associated with Medical Diseases 297 94. Wong KC, Wang Z. Prevalence of type 2 diabetes mellitus of Chinese populations in mainland China, Hong Kong, and Taiwan. Diabetes Res Clin Pract 2006;73(2):126–34. 95. Wong KH, Lee SS, Chan KC. Twenty years of clinical human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) in Hong Kong. Hong Kong Med J 2006;12(2):133–40. 96. Wong WM, Lam KF, Cheng C, et al. Population based study of noncardiac chest pain in southern Chinese: Prevalence, psychosocial factors and health care utilization. World J Gastroenterol 2004;10(5):707–12. 97. World Health Organization. Diabetes mellitus. World Health Organization, 2006. 98. Yan BM, Myers RP. Neurolytic celiac plexus block for pain control in unresectable pancreatic cancer. Am J Gastroenterol 2007;102(2):430-8. 99. Yang EH, Barsness GW, Gersh BJ, et al. Current and future treatment strategies for refractory angina. Mayo Clin Proc 2004;79(10):1284–92.

18

C. Roger GOUCKE

Pain in the Older Person

Introduction

INTRODUCTION EPIDEMIOLOGY PHYSIOLOGICAL, PSYCHOLOGICAL AND PSYCHOSOCIAL CONSIDERATIONS Threshold and tolerance IDENTIFICATION ASSESSMENT PAIN MANAGEMENT OPTIONS Physical Therapies Cognitive or psycho educational therapies Pharmacological therapies INTERVENTIONAL TECHNIQUES POSTOPERATIVE PAIN MANAGEMENT SUMMARY REFERENCES

As the percentage of the population over the age of 65 years increases in both the developed and developing world, so will the number of people in this age group with pain. Unrecognised and poorly managed pain results in an unnecessary and serious decline in the quality of life. This chapter will review the epidemiology of pain in the older person, look at some of the physiological differences that age-related changes bring to pain processing and perception, and the types and causes of pain in the older person, together with its assessment and treatment options.

Epidemiology Population growth varies from country to country with some European countries reporting a negative growth while others continue to increase. In most developed countries with stable populations, the age distribution within the population is changing dramatically. In these countries it is predicted that the population over the age of 65 years will rise from 17.5% to 36.3% by 2050. In addition the population over the age of 80 years is likely to more than triple [40]. This will occur with a relatively stable birth rate. With regard to persistent pain, studies in Australia suggest approximately 17% of adult males and 20% of females report chronic pain. Persistent pain in these studies was defined as pain being present every day for at least 3 months in the preceding 6 months. The prevalence of pain increases with increasing age, such that 30% of females in the 80–84 year age group reported persisting pain [13]. Comparing different prevalence studies on long-term pain, their apparent wide variance is complicated because different researchers have used varying definitions for the terms “long term” or “chronic” [8, 21, 54]. Studies have used the following among others. “Have

300 C. Roger GOUCKE

you any pain now?” “Have you had pain in the last week or month or year?” “Have you had pain for more than 3 months in the last year?” With this background it can be seen that pain in older persons, if not already, will become a significant consideration for health care planning. As people age, accommodation requirements and caring patterns change. It is recognised that not all older patients need the same level of care, some continue to live independently into their 80s and 90s, while others may need low-level hostel-type care. The more frail and disabled older person may continue to be cared for by families, while others will need high-level care including nursing home placement. Educating relatives, nursing home carers and nursing staff will be an ongoing requirement [44]. Associated with increasing age is dementia. It has been estimated that 28% of low-level residential care residents and 60% of high-level residential care residents have a diagnosis of dementia. Cognitive impairment is even more prevalent with 54% of hostel residents and 90% of nursing home residents being cognitively impaired [53, 56, 65]. The detection of pain is significantly reduced in those with severe cognitive impairment [60]. Up to 40% of Australian nursing home residents are totally unable to report pain due to a major cognitive or communicative disability[56]. As people age, they are more susceptible to agerelated degenerative conditions such as osteoarthritis and painful peripheral neuropathy (Table 18.01). However, it is important to remember that pain is not a “normal” component of ageing, it will usually be possible to find a cause whether it be from physical pathology or psychopathology [36, 41]. There are also notable differences in pain-related clinical presentations in the older person. For example, abdominal pain, non-cardiac chest pain, migraine and facial pain are less common [38].

Physiological, psychological and psychosocial considerations Threshold and tolerance A recent meta-analysis of psychophysical measures on pain threshold has clearly demonstrated an

increase in threshold with age [34] such that the pain threshold of the average older adult appears in the top 15% of values seen in younger adults. In this paper, Gibson suggests that the decreased pain sensitivity (increased threshold) might explain the under-reporting of mild pain symptoms, which in turn might increase the risk of undiagnosed disease or injury — for example, “silent” myocardial infarction or perforated bowel [38, 42]. There is also some evidence that the descending inhibitory pain mechanisms are compromised by advancing years [76]. Gibson’s meta-analysis also reviews pain tolerance and shows an age-related decrease in the ability to tolerate severe pain. In summary, the increased threshold, but decreased tolerance of severe pain, highlight the reduced plasticity of the pain pathways in older persons, demonstrating increased vulnerability [37]. Apart from the physiological changes that occur as patients age, psychological and psychosocial effects will also influence the way older persons present with pain. The older person’s beliefs about pain and its treatment may be different to those younger; they and their families may also have different expectations. We know that older persons appear more stoic than other age groups, as do their coping strategies (more praying and hoping) [35, 78]. The effect of retirement and social isolation as their spouses and friends die, together with their loss of independence and looming or actual institutionalisation, will also impact variably on older persons with pain [66].

Identification Because pain is so common in older persons, it may be dismissed as something to be expected and therefore its importance underestimated. In those older persons that can verbally report pain, their report should be accepted and a proper assessment then carried out. In those persons unable to report pain because of cognitive or communicative impairments, different strategies are required. The language we use to ask older persons about their pain may need modifying. It is recommended that words such as “sore” or “hurt” are used rather than the word “pain”. For example “Do you have any ache, soreness or discomfort?” may be more easily understood. The use of open-ended questions

Pain in the Older Person 301

is also more likely to get a useful response. When attempting to quantify the amount or degree of pain, verbal quantifiers are preferable than numerical scales. For example “Is your pain a big problem, a medium problem or a small problem?” Older persons often have attitudinal differences to those of a younger age, often accepting that pain is an expected part of ageing, that pain may suggest worsening disease, that they may be seen as complainers or as distracting physicians from treating the underlying disease [68]. For those persons unable to answer simple questions, usually due to increasing cognitive impairment and dementia, observational charts are available [75]. It is important to identify if the pain behaviour observed occurs at rest or only after a certain activity such as dressing, walking or showering.

Assessment Assessment must begin with a thorough history and clinical examination of the patient (Table 18.02). This process in the elderly can be complex, particularly if there are cognitive or communicative impairments or dementia. It may be useful to use a dementia assessment tool such as the Mini Mental State Evaluation (MMSE) to aid evaluation of mental function [28]. Even for older persons with good cognition, impairments in hearing or vision, or dysphasia and dysarthria following cardiovascular accidents, can be troublesome during the assessment process. For cognitively intact older persons, whether living independently in the community or in residential aged care facilities, any of the self-report pain assessment tools used in younger persons can be used. There is evidence that numerical rating scales are less understood than verbal scales and in some situations help from a health care provider or significant other may be needed. With regard to assessment tools for pain in older persons, they should not be unnecessarily complex because this age group can tire easily. Consideration of cultural and linguistic diversity is also obviously important in multicultural societies. There are a number of recent reviews covering the range of assessment tools available for use in nonverbal patients with dementia. However, none of these tools is well validated or known to be

particularly reliable [43, 79]. The Australian Pain Society in a guideline document for the management of Pain in Residential Aged Care Facilities [39] recommended the use of either the Painad or the Abbey pain scale for patients with dementia who are unable to communicate verbally [1, 75]. These scales use a template for recording behaviour that has been associated with pain. For example: groaning or crying, grimacing or frowning, rocking or guarding a body part, confusion or refusing to eat and the ease of consolability. For those patients with dementia that still retain verbal skills, there is agreement that their verbal pain descriptions should be accepted. The Australian Pain Society has recommended that for cognitively intact older persons that a modified Brief Pain Inventory be used [18, 39]. There is also agreement that multidimensional tools are required to ensure that as many facets of pain on the older person’s life can be assessed. A good assessment tool should cover pain intensity, quality, variability and course thoroughly. The effect of pain on the individual’s life must also be assessed; this should include its effect on function and quality of life. Depression (including

Table 18.01 Factors and conditions associated with persistent non-cancer pain in older persons • Low back disorders (vertebral compression fractures, facet arthropathies, spinal canal stenosis) • Degenerative joint disease (osteoarthritis) • Rheumatoid and other inflammatory arthritides • Crystal induced arthropathies (gout, calcium pyrophosphate) • Pressure and other skin ulcers • Chronic leg cramps • Peripheral vascular disease (rest pain, claudication) • Amputations (stump pain, phantom limb pain) • Post-stroke pain syndromes • Neuropathic pain (diabetes, postherpetic neuralgia, carpal tunnel syndrome, trigeminal and occipital neuralgia) • Headache • Oral and dental pathology • Angina • Constipation • Immobility, contracture • Mood disorders Modified from Ferrell B, Pain evaluation and management 1995 and AMDA Clinical Practice Guideline 1999 [7, 25].

302 C. Roger GOUCKE

the increased risk of suicide in depressed older persons), anxiety, sleep disruption, appetite and interruption or disruption of activities of daily living, because of or as a direct effect of pain, need to be recorded [5, 27]. As we age, increasing numbers of comorbid medical conditions develop such as ischaemic heart disease Table 18.02

Factors relevant to a pain assessment

Pain history • When pain began • Severity • Aggravating and relieving factors • Site • Quality • Radiation General medical history • Relevant diseases (e.g. dementia, arthritis, vascular, gastrointestinal, renal) • Associated symptoms (e.g. nausea) • Allergies Physical examination • Sites of reported pain and referred pain • The musculoskeletal and neurological systems • Signs of arthritis • Sensory changes (including hyperalgesia and allodynia) Physical impact of pain • Impact of pain on activities of daily living • Spontaneous pain • Evidence of activity • Avoidance of activity • Comfort on movement • Functional assessment Psychosocial situation • Coping resources • Beliefs about the cause(s) of the pain • Cognitive state • Family expectations and beliefs about pain and stress • Presence of anxiety and depression • Effect on sleep • Suicidal thoughts Social impact of pain • Relationships • Activities Review of medications and other treatments • Treatments that have been tried • Effectiveness of current therapies Modified from the National Health and Medical Research Council Acute Pain Scientific Evidence 2005 and the American Geriatrics Society panel guidelines on Pain in Older Persons 2002 [5, 9].

and degenerative joint disease. These conditions may or may not be painful. Assessing the contribution of this incidental pathology may prove difficult, for example, on radiological evidence of degenerative change in lumbar vertebra.

Pain Management Options Not all older persons living in the community need help to manage their pain; indeed many cope very well and even minimise their discomfort; others manage with minimal help. However, when pain becomes “bothersome”, a number of clinical practice guidelines are now available [5, 7, 39]. It must be noted that the evidence base on which these recommendations are made is limited, mainly because of the dearth of research on pain-related topics that have actually included older persons. While pharmacological management of pain in older persons is often one of the first-line therapies for persistent pain, efficacy is likely to be improved when drug therapy is combined with nonpharmacological treatments.

Physical therapies Exercise within the physical capacity of the individual should be the first choice of physical therapy. Isotonic exercise involves resisted contractions of major muscle groups through a prescribed joint range. It has the advantage that it can be done lying, sitting and standing; it is different to isometric exercise and the traditional aerobic exercise recommended for cardiovascular fitness. In isotonic exercise, the resistance can be varied (for example: highor low-weight sandbags or differing strengths of elastic ribbon) and the number of repetitions can be monitored and, if necessary, supervised. There is most evidence supporting the value of isotonic and aerobic exercises, which have been shown to reduce pain in musculoskeletal disorders by around 30% [4, 14, 30, 31]. This type of exercise also has a positive effect on depressed mood [69] and sleep [70]. Aerobic exercise such as walking or cycling involves sustained repetitive movements of large muscle groups. However, it may be precluded in the elderly because of frailty and comorbid conditions. It has long been recognised that graduated exercise can improve claudication distance in individuals with peripheral vascular disease [50]. Stretching

Pain in the Older Person 303

exercises are often recommended for individuals, whether old or young; however, there is a lack of evidence in the literature to support this activity to improve pain or mood. Superficial heat in the form of hot packs or blankets has been reported as a comfort measure [64], but there is lack of evidence for pain relief. There are always concerns of damage to skin and deeper tissues, especially in patients with decreased cognitive function and dementia. Superficial cold likewise cannot be recommended for pain relief in the older person [15]. Transcutaneous electrical nerve stimulation (TENS) is widely used in the management of chronic pain in adults. It has some evidence for analgesic activity in degenerative joint disease. It is a cheap and simple technique and could be used in those older persons who are able to report the stimulation sensation [16, 57, 62]. There is evidence that if used intermittently for at least 40 minutes at a time, that up to 30 minutes analgesia can be achieved [17]. TENS machines should produce a firm but comfortable stimulation over the area of perceived pain. The precise parameters need to be determined by trial and error (so cognitive function needs to be reasonable) both low frequency or “acupuncturelike TENS” of 2 – 5 Hz or high frequency 80 – 100 Hz appear to be effective [16]. Acupuncture is widely used for the treatment of chronic pain in both Western and Traditional Chinese Medicine, there is current interest in explaining its apparent efficacy and increasing trials to demonstrate this. In general though, it is still considered a complementary therapy by Western practitioners, and its use for chronic pain problems can make application time consuming. Therefore, it may not be cost-effective or practical [12, 67, 77].

Cognitive or psycho educational therapies Pain is a sensory and emotional experience, consequently when a nociceptive or neuropathic source either cannot be found or even if found cannot be “cured”, it is current practice to address these components of pain by using a psychoeducational approach. Cognitive (thought) behavioural (actions) therapy (CBT) is the technique most often used to apply

Table 18.03

Cognitive behavioural therapy interventions

• Modification of beliefs and attitudes about pain • Teaching new coping methods • Stress reduction techniques • Goal setting • Planned behavioural reactivation • Pacing of physical activity • Education about the nature of pain and its consequences on mood, function and quality of life • Relaxation training • Distraction and imagery techniques

psycho-educational therapies to patients (Table 18.03). There is good evidence for using these techniques in adults with persistent pain but also specifically in older persons [5, 19, 24, 73]; as well as reduced pain, increased coping skills, engagement in social activity and overall quality of life have been described. This type of therapy must be delivered by trained therapists and will usually include a clinical psychologist with support from other members of the health care team, in particular nursing staff to help reinforce the therapy. The psychological components of persistent pain, for example, anxiety and depression will also be addressed as part of a CBT approach. Typical CBT programmes run over a period of weeks and can be full time or part time, residential or with day attendance. They consist of a structured programme which, while often generic, can be individualised depending on the precise issues raised between the patient and therapist [24, 46, 74]. More detail about CBT can be found in Chapter 38.

Pharmacological therapies Paracetamol Paracetamol is the most recommended medication for first-line management of mild to moderate pain in older persons, and can also be recommended for additional use in severe pain when opioids are being used [5, 39]. The maximum dose of 4 g per day appears safe unless there is a history of high alcohol intake, liver dysfunction, dehydration, prolonged fasting or poor nutrition, when the dose should be decreased. Paracetamol is available in combination

304 C. Roger GOUCKE

with many other compounds and available over the counter, consequently a thorough medication history may be necessary to identify non-prescribed doses

Non-steroidal anti-inflammatory drugs (NSAIDs) Cyclo-oxygenase (COX-1) and (COX-2) drugs are also commonly prescribed for the elderly. While they have both analgesic and anti-inflammatory effects, they also have significant and serious side effects. Both these groups of drugs should be used with caution in older persons. They are associated with an increased risk of upper gastrointestinal (GI) haemorrhage, renal dysfunction with fluid and sodium retention, increased blood pressure, peripheral oedema and reduced glomerular filtration. If used in combination with angiotensin converting enzyme inhibitors and diuretics, the so-called “triple whammy” effect can occur with significant risk of drug induced renal failure [3]. As with many drugs in the elderly, if selective COX2 inhibitors and traditional NSAIDs are indicated, the lowest dose for the shortest duration should be prescribed. Some of the risk factors for GI bleeding include age over 65 years, previous GI bleed and concomitant use with medications such as warfarin, aspirin, clopidogrel and corticosteroids. The GI side effects of these drugs are becoming clearer; there is evidence to suggest that COX-2 inhibitors are less damaging than traditional NSAIDs (even with a proton pump inhibitor or histamine-2 receptor antagonist) to the gastric and lower bowel mucosa [58]. Debate has arisen recently about their prothrombotic effects. While rofecoxib has been withdrawn from the market, attention has focused on this particular side effect of all these drugs. Evidence is available demonstrating as much risk of a myocardial infarction for patients on diclofenac as there was for rofecoxib [10]. There is also a suggestion that the risk of myocardial infarction is not necessarily due to duration of the drug’s use, as appears to be the case with the other NSAID-related side effects. Levesque demonstrated a median time to myocardial infarction with the use of rofecoxib of 9 days [51].

Opioids There have been a number of systematic reviews and meta-analyses of randomised controlled trials (RCTs) on the use of opioids in chronic non-cancer pain published in the last few years [23, 32, 45]. While not specifically targeted at the older person, the studies have included conditions such as postherpetic neuralgia, painful peripheral diabetic neuropathy and osteoarthritis, all of which are more common in the older person. In these reviews, it was difficult to determine the effects of opioids on functional or quality of life outcomes. These meta-analyses have shown that there was a significant placebo effect apparent during the trials, with the mean decrease in pain intensity being around 30% for the active arm and between 15–30% for the placebo arm. The mean decrease in visual analogue scale pain score was 15/100. Withdrawal rates in general were high with 5–10% of patients leaving the study because of lack of opioid efficacy (20% for placebo) and between 20% and 30% withdrawing due to opioid related side effects (5–15% for placebo). In general, side effects were common with 50–80% of patients developing at least one opioid-related side effect (30–60% for placebo). Only 30% of the RCT patients remained on “long-term” opioid therapy. Older persons tend to be more sensitive to opioids and appear to experience greater and more prolonged pain relief [29]. They are, however, more prone to side effects. In a systematic review of RCTs by Moore and McQuay (age groups not specified), the most common opioid-related adverse events were dry mouth (25%), nausea (21%) and constipation (15%) [59]. Dizziness (14%), drowsiness and somnolence (14%), pruritis (13%) and vomiting (10%) were also common; however, there was a high incidence of these symptoms in the placebo groups as well [59]. In systematic reviews by Kalso et al. [45] and Eisenberg et al. [23], the number needed to harm (NNH) for opioids in the treatment of chronic non-cancer pain were in the following ranges: nausea 3.6–5.0, constipation 3.4– 4.6, drowsiness 5.3, vomiting 6.2–8.1, dizziness 6.7–8.2 and itchiness 13.

Tramadol Tramadol is an atypical opioid analgesic combining mu, noradrenergic and serotonergic receptor agonist effects. Tramadol is effective in

Pain in the Older Person 305

the treatment of moderately severe chronic pain, particularly neuropathic pain such as postherpetic neuralgia and painful diabetic neuropathy [26]. Tramadol may produce less constipation, respiratory depression, dependence, abuse and diversion compared with standard opioids [2, 63]. Tramadol has a significant side-effect profile in some people especially the elderly with nausea, dizziness, delirium and hallucinations having been reported. There are some concerns particularly when higher doses of tramadol are combined with tricyclic antidepressants or selective serotonin reuptake inhibitors with regard to provoking fits in patients who have a reduced seizure threshold and the possibility of the development of a serotonergic syndrome [47, 48].

Buprenorphine Although there is significant confusion in the literature, buprenorphine is most commonly classified as a (partial) mu agonist/kappa antagonist. However, this is based largely on animal data and may not necessarily apply in the clinical setting. There is some consensus that in lower doses commonly used in clinical pain management, buprenorphine acts more like a “full” mu agonist. The partial agonist effect only occurs at very high doses as used in the treatment of opioid addiction [20]. The use of buprenorphine in the treatment of pain in older persons has increased significantly over recent years, mainly as a transdermal system in doses of 5–70 mcg/h. Transdermal buprenorphine is effective in the treatment of non-cancer pain, based largely on open-label surveillance data [52, 71], and a limited number of randomised placebo controlled trials [72]. There is limited evidence of its efficacy in older persons In summary then for the use of opioids in older persons, the recommendations are to use low doses for as short a period of time as is practical, not to use opioids in isolation — always combine with non-opioid analgesics and always implement non-drug treatment strategies. Treat potential side effects such as constipation and nausea proactively.

Adjuvant analgesics Paracetamol should be considered the most widely prescribed adjuvant drug, but usually this term refers to the use of drugs not normally associated with analgesia. These drugs are usually prescribed

for neuropathic pain and include medications such as antidepressants and antiepileptic agents. These drugs should be selected on their evidence for efficacy for the underlying condition, their side-effect profile, together with the cost and availability. The older tricyclic antidepressants have a long record of use but have side effects especially in the older person. Perhaps the best tolerated is nortriptyline at a low dose of 5–10 mg at night. Antiepileptic medications such as carbamazepine have long been used to treat trigeminal neuralgia and newer drugs such as gabapentin and pregabalin have an increasing evidence base for efficacy in neuropathic pain and are better tolerated in the older person [61].

Interventional Techniques There are a range of interventional options that have validity for persistent pain and may be considered in the older person. Conditions likely to benefit would include trigeminal neuralgia, peripheral vascular disease, acute zoster and persistent spinal pain. Nerve blocks of the major divisions of the trigeminal nerve using glycerol or balloon compression or microvascular decompression via posterior fossa craniectomy have a place if medical therapy fails and have recently been reviewed [11]. A wide range of spinal injections including facet rhizotomy for back pain and epidural steroid injections for lumbar radicular symptoms may also be of value [6, 49].

Postoperative Pain Management Advances in anaesthetic and surgical techniques together with the changing demographics of the population mean that more surgical procedures are being offered to older persons. The presence of coexistent diseases and multiple medications make the management of postoperative pain more challenging. A recent review of the scientific evidence of the management of acute pain identifies patient

306 C. Roger GOUCKE

controlled and epidural analgesia as being more effective in older persons than conventional opioid regimens [9, 55]. The review also notes the agerelated decrease in opioid requirements allowing for significant inter-individual differences. The verbal descriptor scale in the acute pain setting may be more reliable than other scales particularly in those patients with cognitive impairment [33].

•

• •

Summary • • • • • • •

Pain is common in older persons Assessment can be complex especially in those with cognitive impairment and dementia Pain threshold is increased whilst tolerance may be decreased The language of pain can be different; patients use words such as sore, hurt, ache rather than pain Assessment tools should be simple and multidimensional A thorough history and examination will usually find a cause for the pain; old age on its own does not cause pain Targeted physical therapies along with

cognitive behavioural therapy should be considered in all patients Paracetamol is the first line drug of choice; NSAIDs if used should be low dose and for the shortest duration possible to minimise side effects Opioids in low dose and for defined duration have value; prophylaxis of constipation is essential Patient controlled and epidural analgesia are effective in older persons in the postoperative period.

Successful ageing doing the best one can with what one has Pamela Melding in a forward to “Pain in older persons” [36] Further reading: Pain in Older Persons, Progress in Pain Research and Management volume 35, 2005, IASP press [36]. Smith, HS Ed. Pain Management. Clinics in Geriatric Medicine (2008) [22]

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Abbey J, Piller N, De Bellis A, et al. The Abbey pain scale: A 1-minute numerical indicator for people with end-stage dementia. Int J Palliat Nurs 2004;10(1):6–13. Adams EH, Breiner S, Cicero TJ, et al. A comparison of the abuse liability of tramadol, NSAIDs, and hydrocodone in patients with chronic pain. J Pain Symptom Manage 2006;31(5):465–76. ADRAC. ACE inhibitor, diuretic and NSAID: A dangerous combination, 2003. Afable RF, Ettinger WH Jr. Musculoskeletal disease in the aged. Diagnosis and management. Drugs Aging 1993;3(1):4959. AGS Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. J Am Geriatr Soc 2002;50:S205–S224. Ahmad M, Goucke CR. Management strategies for the treatment of neuropathic pain in the elderly. Drugs Aging 2002;19(12):929–45. AMDA. Pain Management in the Long Term Care Setting. San Diego: AMDA, 2003. Andersson HI, Ejlertsson G, Leden I, et al. Chronic pain in a geographically defined general population: Studies of differences in age, gender, social class, and pain localization. Clin J Pain 1993;9(3):174–82. ANZCA. Acute Pain Management: Scientific Evidence. Australian and New Zealand College of Anaesthetists, 2005. Bandolier. MI, COXIBs, and NSAIDs, 2006. Bennetto L, Patel NK, Fuller G. Trigeminal neuralgia and its management. BMJ 2007;334(7586):201–5. Berman BM, Lao L, Langenberg P, et al. Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: A randomized, controlled trial. Ann Intern Med 2004;141(12):901–10. Blyth FM, March LM, Brnabic AJ, et al. Chronic pain in Australia: A prevalence study. Pain 2001;89(2-3):127–34.

Pain in the Older Person 307

14. Bravo G, Gauthier P, Roy PM, et al. Impact of a 12-month exercise program on the physical and psychological health of osteopenic women. J Am Geriatr Soc 1996;44(7):756–62. 15. Brosseau L, Yonge KA, Robinson V, et al. Thermotherapy for treatment of osteoarthritis. Cochrane Database Syst Rev 2003;(4):CD004522. 16. Carroll D, Moore RA, McQuay HJ, et al. Transcutaneous electrical nerve stimulation (TENS) for chronic pain. Cochrane Database Syst Rev 2001;(3):CD003222. 17. Cheing GL, Tsui AY, Lo SK, et al. Optimal stimulation duration of TENS in the management of osteoarthritic knee pain. J Rehabil Med 2003;35(2):62–8. 18. Cleeland C. Measurement of pain by subjective report. In Chapman C, Loeser J, eds. Issues in Pain Measurement. New York: Raven Press, 1989. 19. Cook AJ. Cognitive-behavioral pain management for elderly nursing home residents. J Gerontol B Psychol Sci Soc Sci 1998;53(1):P51–9. 20. Cowan A, Friedrichs E, Strassburger W, Rafa RB. Basic pharmacology of buprenorphine In Budd K RR, ed. Buprenorphine — the Unique Opioid Analgesic. Pharmacology and Clinical Application. Stuttgart: Georg Thieme Verlag KG, 2005;3–21. 21. Crook J, Rideout E, Browne G. The prevalence of pain complaints in a general population. Pain 1984;18(3):299– 314. 22. Deane G, Smith HS. Overview of pain management in older persons. Clin Geriatr Med 2008;24(2):185–201. 23. Eisenberg E, McNicol ED, Carr DB. Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: Systematic review and meta-analysis of randomized controlled trials. JAMA 2005;293(24):3043– 52. 24. Ersek M, Turner JA, McCurry SM, et al. Efficacy of a self-management group intervention for elderly persons with chronic pain. Clin J Pain 2003;19(3):156–67. 25. Ferrell BA. Pain evaluation and management in the nursing home. Ann Intern Med 1995;123(9):681–7. 26. Finnerup NB, Otto M, McQuay HJ, et al. Algorithm for neuropathic pain treatment: An evidence based proposal. Pain 2005;118(3):289–305. 27. Flor H, Fydrich T, Turk DC. Efficacy of multidisciplinary pain treatment centers: A meta-analytic review. Pain 1992;49(2):221–30. 28. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12(3):189–98. 29. Forman WB. Opioid analgesic drugs in the elderly. Clin Geriatr Med 1996;12(3):489–5. 30. Fransen M, McConnell S, Bell M. Exercise for osteoarthritis of the hip or knee. Cochrane Database Syst Rev 2003;(3): CD004286. 31. Fransen M, McConnell S, Bell M. Therapeutic exercise for people with osteoarthritis of the hip or knee. A systematic review. J Rheumatol 2002;29(8):1737–45. 32. Furlan AD, Sandoval JA, Mailis-Gagnon A, et al. Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects. Can Med Assoc J 2006;174(11):1589–94. 33. Gagliese L, Katz J. Age differences in postoperative pain are scale dependent: A comparison of measures of pain intensity and quality in younger and older surgical patients. Pain 2003;103(1-2):11–20. 34. Gibson S. Proceedings of the 10th World Congress on Pain, 2003. 35. Gibson S, Chambers C. Pain across the life span: A developmental perspective. In Hadjistavropoulis T, ed. Pain: Psycholgical Perspectives. Mahwah: Lawrence Erlbaum, 2003. 36. Gibson SJ, Weiner DK, eds. Pain in Older Persons, Progress in Pain Research and Management, Vol. 35. Seattle: IASP press, 2005. 37. Gibson SJ, Farrell M. A review of age differences in the neurophysiology of nociception and the perceptual experience of pain. Clin J Pain 2004;20(4):227–39. 38. Gibson SJ, Helme RD. Age-related differences in pain perception and report. Clin Geriatr Med 2001;17(3):433–56. 39. Goucke R, ed. Pain in Residential Aged Care Facilities: Management Strategies. Sydney: Australian Pain Society, 2005. 40. Global Population at a Glance: 2002 and Beyond. International Belief. US Census Bureau. International Database 2004 Wp02, http://www.census.gov/ipc/prod/wp02/wp02-1.pdf 41. Harkins SW, Davis MD, Bush FM, et al. Suppression of first pain and slow temporal summation of second pain in relation to age. J Gerontol A Biol Sci Med Sci 1996;51(5):M260–5. 42. Helme RD, Gibson SJ. The epidemiology of pain in elderly people. Clin Geriatr Med 2001;17(3):417–31. 43. Herr K, Bjoro K, Decker S. Tools for assessment of pain in nonverbal older adults with dementia: A state-of-the-science review. J Pain Symptom Manage 2006;31(2):170–92. 44. Higgins I, Madjar I, Walton JA. Chronic pain in elderly nursing home residents: The need for nursing leadership. J Nurs Manag 2004;12(3):167–73.

308 C. Roger GOUCKE

45. Kalso E, Edwards JE, Moore RA, et al. Opioids in chronic non-cancer pain: Systematic review of efficacy and safety. Pain 2004;112(3):372–80. 46. Kerns RD, Otis JD, Marcus KS. Cognitive-behavioral therapy for chronic pain in the elderly. Clin Geriatr Med 2001;17(3):503–23. 47. Kitson R, Carr B. Tramadol and severe serotonin syndrome. Anaesthesia 2005;60(9):934–5. 48. Labate A, Newton MR, Vernon GM, et al. Tramadol and new-onset seizures. Med J Aust 2005;182(1):42–3. 49. Lavelle WF, Lavelle ED, Smith HS. Interventional techniques for back pain. Clin Geriatr Med 2008;24(2):345–68. 50. Leng GC, Fowler B, Ernst E. Exercise for intermittent claudication. Cochrane Database Syst Rev 2000;(2):CD000990. 51. Levesque LE, Brophy JM, Zhang B. Time variations in the risk of myocardial infarction among elderly users of COX-2 inhibitors. Can Med Assoca J 2006;174(11):1563–9. 52. Likar R, Kayser H, Sittl R. Long-term management of chronic pain with transdermal buprenorphine: A multicenter, open-label, follow-up study in patients from three short-term clinical trials. Clin Ther 2006;28(6):943–52. 53. Madjar I, Higgins I. Unrecognised pain in nursing home residents. In DoV, ed Veterans Health Handbook, 1997;13–5. 54. Magni G, Marchetti M, Moreschi C, et al. Chronic musculoskeletal pain and depressive symptoms in the National Health and Nutrition Examination. I. Epidemiologic follow-up study. Pain 1993;53(2):163–8. 55. Mann C, Pouzeratte Y, Boccara G, et al. Comparison of intravenous or epidural patient-controlled analgesia in the elderly after major abdominal surgery. Anesthesiology 2000;92(2):433–41. 56. McClean WJ, Higginbotham NH. Prevalence of pain among nursing home residents in rural New South Wales. Med J Aust 2002;177(1):17–20. 57. Milne S, Welch V, Brosseau L, et al. Transcutaneous electrical nerve stimulation (TENS) for chronic low back pain. Cochrane Database Syst Rev 2001;(2):CD003008. 58. Moore RA, Derry S, Phillips CJ, et al. Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: Review of clinical trials and clinical practice. BMC Musculoskelet Disord 2006;7:79. 59. Moore RA, McQuay HJ. Prevalence of opioid adverse events in chronic non-malignant pain: Systematic review of randomised trials of oral opioids. Arthritis Res Ther 2005;7(5):R1046–51. 60. Morrison RS, Siu AL. A comparison of pain and its treatment in advanced dementia and cognitively intact patients with hip fracture. J Pain Symptom Manage 2000;19(4):240–8. 61. Nikolaus T, Zeyfang A. Pharmacological treatments for persistent non-malignant pain in older persons. Drugs Aging 2004;21(1):19–41. 62. Osiri M, Welch V, Brosseau L, et al. Transcutaneous electrical nerve stimulation for knee osteoarthritis. Cochrane Database Syst Rev 2000;(4):CD002823. 63. Preston KL, Jasinski DR, Testa M. Abuse potential and pharmacological comparison of tramadol and morphine. Drug Alcohol Depend 1991;27(1):7–17. 64. Robinson SB, Weitzel T, Henderson L. The Sh-h-h-h Project: Nonpharmacological interventions. Holist Nurs Pract 2005;19(6):263–6. 65. Rosewarne R, Bruce A, McKenna M. Dementia programme effectiveness in long-term care. Int J Geriatr Psych 1997;12(2):173–82. 66. Roy R. Social Relations and Chronic Pain. New York: Academic/Plenum, 2001. 67. Salter GC, Roman M, Bland MJ, et al. Acupuncture for chronic neck pain: A pilot for a randomised controlled trial. BMC Musculoskelet Disord 2006;7: 99. 68. Sengstaken EA, King SA. The problems of pain and its detection among geriatric nursing home residents. J Am Geriatr Soc 1993;41(5):541–4. 69. Singh NA, Clements KM, Fiatarone MA. A randomized controlled trial of progressive resistance training in depressed elders. J Gerontol A Biol Sci Med Sci 1997;52(1):M27–35. 70. Singh NA, Clements KM, Fiatarone MA. A randomized controlled trial of the effect of exercise on sleep. Sleep 1997;20(2):95–101. 71. Sittl R. Transdermal buprenorphine in the treatment of chronic pain. Expert Rev Neurother 2005;5(3):315–23. 72. Sorge J, Sittl R. Transdermal buprenorphine in the treatment of chronic pain: Results of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Clin Ther 2004;26(11):1808–20. 73. Sorkin BA, Rudy TE, Hanlon RB, et al. Chronic pain in old and young patients: Differences appear less important than similarities. J Gerontol 1990;45(2):P6–8. 74. Turner J, Keefe F. Cognitive-behavioral therapy for chronic pain. In Refresher Course Syllabus. Seattle: IASP Press, 1999. 75. Warden V, Hurley AC, Volicer L. Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD) scale. J Am Med Dir Assoc 2003;4(1):9–15. 76. Washington LL, Gibson SJ, Helme RD. Age-related differences in the endogenous analgesic response to repeated cold water immersion in human volunteers. Pain 2000;89(1):89–96.

Pain in the Older Person 309

77. White A, Foster NE, Cummings M, et al. Acupuncture treatment for chronic knee pain: A systematic review. Rheumatology 2007;46(3):384–90. 78. Yong HH, Gibson SJ, Horne DJ, et al. Development of a pain attitudes questionnaire to assess stoicism and cautiousness for possible age differences. J Gerontol B Psychol Sci Soc Sci 2001;56(5):P279–84. 79. Zwakhalen SM, Hamers JP, Abu-Saad HH, et al. Pain in elderly people with severe dementia: A systematic review of behavioural pain assessment tools. BMC Geriatr 2006;6:3.

19

George CHALKIADIS

Pain in Children and Adolescents

Introduction INTRODUCTION NEURODEVELOPMENTAL ASPECTS PHARMACOLOGICAL ASPECTS ANATOMICAL CONSIDERATIONS

The last 30 years have seen an explosion in research and publications on pain in childhood and adolescence. Attention has focused on several aspects including the developing nociceptive system, acute, persistent, procedural and cancer pain management. Growth and development distinguish children from adults. Clinically, an appreciation of the physiological, anatomical and psychosocial developmental changes during childhood is important in the assessment and management of pain.

HISTORICAL BACKGROUND DO NATIONAL GUIDELINES IMPROVE PAIN MANAGEMENT? PAIN ASSESSMENT ACUTE PAIN MANAGEMENT Drugs Regional blocks and use of local anaesthetics Special considerations (burns and cerebral palsy) PROCEDURAL PAIN MANAGEMENT PERSISTENT PAIN MANAGEMENT A WORLD PERSPECTIVE

Neurodevelopmental Aspects The structural components necessary for pain perception start to form at about 17 weeks and become established from 26 weeks’ gestation [54]. Pituitary-adrenal, sympatho-adrenal and circulatory stress responses to physical insults have been demonstrated in the human foetus from 18–20 weeks [53]. Noxious stimulation causes detectable stress response in the foetus from at least 23 weeks’ gestation [64]. There is debate whether hormonal stress responses and withdrawal reflexes to invasive procedures prove the existence of foetal pain, as they can be elicited by non-painful stimuli and occur without conscious processing [91]. Noxious stimulation (heel lance) is transmitted to the preterm infant cortex from 25 weeks [141]. Opioid receptors are abundant in the foetal spinal cord and brain stem by 20 weeks [95, 129]. There is evidence that intravenous fentanyl attenuates the foetal response to intrahepatic needling [53]. These observations have implications regarding surgery in premature neonates, late abortion and foetal surgery.

312 George CHALKIADIS

Laboratory studies in rats have shown that the immaturity of sensory processing within the newborn spinal cord leads to lower thresholds for excitation and sensitisation. Foetal spinal cord sensory neurones that respond to noxious stimuli have larger receptive fields than in adults [55]. Endogenous descending inhibitory pathways are not fully developed until mid-infancy raising the possibility that neonates may be more sensitive to noxious stimuli than older children. The plasticity of both peripheral and central sensory connections in the neonatal period means that early damage in infancy can lead to prolonged structural and functional alterations in pain pathways that may persist into adulthood [16]. Clinically, increased saliva cortisol [154] and pain behaviour [151, 154] have been demonstrated in response to vaccination, in neonates circumcised without analgesia or born by difficult delivery.

Pharmacological Aspects The administration of analgesic drugs in children requires careful pharmacokinetic and pharmacodynamic considerations. The neonatal period and early infancy are periods of rapid growth and development. Pharmacokinetic analyses allow the use of size as the primary co-variate, and have enabled exploration of the effects of age, facilitating the comparison of neonatal data with adult data [7]. Generally, clearance increases with age, necessitating care with dosage in neonates and young infants.

Anatomical Considerations In neonates and young infants, the epidural fat is spongy and gelatinous in appearance with distinct spaces between individual fat globules. With increasing age, fat becomes more tightly packed and fibrous [157]. The clinical implications of this difference in anatomy, is that an epidural catheter can be inserted via the caudal route and easily threaded cephalad, so that the tip lies in the thoracic epidural space [23].

Historical Background of Pain Management in Children For many years, children were denied adequate pain relief due to outmoded beliefs including that: • Newborn infants do not experience pain [128] • Children rarely require drugs for pain [150] • Pain is merely a symptom, and not necessarily harmful in itself [14] • Effective analgesia makes diagnosis difficult or impossible [68, 86] • Effective analgesia delays discharge from hospital • Pain is an inevitable consequence of surgery • Pain relief is dangerous. These beliefs in turn led to variability in prescribing practices [100]: • Postoperative analgesia was frequently not prescribed • Prescribed doses were too small or too infrequent. Compounding these issues, prescribed analgesia was administered by unpleasant routes (intramuscular or rectal) that led to children refusing pain relief. Pain assessment and analgesia were low priorities for hospitals, surgeons, anaesthetists and nurses [67]. Most importantly, no health care provider was accountable for poor analgesia. Along with changing attitudes of paediatric anaesthetists to pain relief [43], the mid-1980s saw the establishment of paediatric pain services in the United States, the United Kingdom, Australia and France to facilitate the administration of effective analgesia to children utilising more sophisticated techniques [21]. These improvements in pain management have not been adopted worldwide, even among developed nations. A recent survey of 383 German anaesthesia departments of hospitals in which paediatric surgery was performed revealed that 20.9% never administered intravenous opioids to children and that 15.4% regularly prescribed intramuscular analgesia [144]. In lesser developed countries, lesser standards and reduced availability of anaesthesia and postoperative nursing care along with cultural attitudes to opioid analgesia make it less likely that

Pain in Children and Adolescents 313

effective continuous infusion analgesic techniques are used. Nevertheless, the more widespread use of single-shot nerve blocks and caudal epidural blocks in combination with balanced oral analgesia have the potential to improve postoperative analgesia for children undergoing minor surgery.

Do National Guidelines Improve Pain Management? Although national guidelines on pain management [114, 155, 164] may influence the accreditation of hospitals for training [180], they do not ensure the commitment of all hospitals [70, 126]. In the USA, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) is an independent not-for-profit organisation that sets health care standards. The JCAHO standards require that hospitals assess, treat and document patients’ pain, guarantee the competence of their staff in pain assessment and management, and educate patients and families about effective pain management [123]. Adherence to these standards determines in part, accreditation of health care facilities. It would seem that the most effective way to effect organisational change is, therefore, to institute standards which hospitals must adhere to in order to achieve and maintain accreditation. These standards indicate strongly that the assessment and treatment of acute pain is no longer optional. It is a basic standard of care.

Pain Assessment Many centres have adopted pain assessment as the fifth vital sign, requiring nurses to assess pain and document this on the main observation chart. This increases the likelihood that adequate analgesia is administered to children in pain. A variety of pain assessment tools is available [35, 146]. Composite tools incorporating physiological and behavioural indicators (CRIES and PIPP) are available for premature and term neonates [103], while behavioural scales such as the FLACC (faces, legs, activity, cry and consolability) observational pain tool can be utilised in infants and cognitively intact preverbal children [107]. The revised FLACC has shown reliability and validity postoperatively

in children with cognitive impairment [96]. More complex tools are available to assess pain in children and adolescents with cognitive impairment [26]. In older cognitively intact children, self-report scales such as the Faces Pain Scale — revised [71], WongBaker Faces Pain Scale [182], visual analogue scales (e.g. 10-cm horizontal or vertical line or numerical rating scales (0–10)) can be used. For an individual institution, it is most important to select appropriate pain assessment tools that are culturally relevant and which can be used to assess pain in neonates, preverbal children, those with cognitive impairment and older children capable of self-report. Standardisation of the tools adopted in any given institution facilitates nurse and medical staff education, and communication about pain. The Wong-Baker Faces Pain Scale, visual analogue scale and Faces Pain Scale Revised have been assessed in Thai children and showed moderate to good correlation and moderate agreement [115].

Acute Pain Management In developed countries, intramuscular injections have become outmoded. Multimodal analgesia is utilised to optimise analgesia in the perioperative setting. Strong analgesia is indicated after major surgery, trauma or children with cancer pain. Generally, this may include alone or in combination, intravenous opioid infusion, intravenous ketamine infusion, a regional technique, intermittent oral or intravenous tramadol, oral or intravenous paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). As pain decreases, these analgesics can be gradually weaned. Most patients are discharged with weaker analgesics such as paracetamol, ibuprofen and tramadol if required. Analgesics commonly prescribed in paediatric patients and their dosage regimens are summarised in Table 19.01.

Drugs for acute pain Paracetamol Paracetamol is the first-line analgesic for mild to moderate pain in children. Clearance increases with postconception age [4] from 27 weeks (1.87 l.h-1 per 70 kg) to reach 84% of the mature value (16.3 l.h-1) by 12 months of age [8, 184]. As paracetamol may

314 George CHALKIADIS

Table 19.01

Commonly used analgesic drug doses

Drug

Dose

Cautions

Paracetamol

15 mg/kg q6h (max 90 mg/kg/day) in children >44 wks postconception age

Prescribe according to lean body mass Use with caution in patients with elevated liver enzymes, jaundice, glutathione depletion, malnutrition

12.5 mg/kg q6h in premature neonates 32–36 wks postconception age 10 mg/kg q6h in premature neonates 28–32 wks postconception age Codeine

0.5–1 mg/kg q4h

Oxycodone

0.1–0.2 mg/kg q4h

Morphine

IV bolus dose: 0.05–0.1 mg/kg

Poor metabolisers

PCA bolus 20 mcg/kg, lockout 5 min, background 5 mcg/kg/h IV infusion: 10–40 mcg/kg/h Hydromorphone

PCA bolus 2–4 mcg/kg, lockout 5 min, background 1–2 mcg/kg/h

Fentanyl

Intraoperative bolus: 1–5 mcg/kg IV infusion up to 1.2 mcg/kg/h with 0.3 mcg/kg bolus q5min prn PCA bolus 0.3 mcg/kg, lockout 5 min, background 0.3 mcg/kg/h

Remifentanil

Initial bolus: 1 mcg/kg Infusion: 0.05–0.2 mcg/kg/min

Ketamine (analgesia)

10–40 mcg/kg/h by infusion

Ibuprofen

10 mg/kg q6h

Diclofenac

Oral: 1 mg/kg q8h

Dose >1 mcg/kg may cause apnoea

Rectal: 0.5 mg/kg q12h Naproxen

7 mg/kg (max 500 mg) q12h

Indomethacin

Oral: 0.25–1 mg/kg q8h Rectal: 1 mg/kg q12h

Ketorolac

IV: 0.2 mg/kg (max 10 mg) q6h

Ensure adequate hydration

Parecoxib

0.5 mg/kg

Bupivacaine Levobupivacaine Ropivacaine

2.5 mg/kg single shot Infusion up to 0.4 mg/kg/h

Tramadol

1-2 mg/kg 6h prn

Amitriptyline

Up to 1 mg/kg

Prolonged QT syndrome Gradually increase dose to avoid side effects

Gabapentin

Starting dose 10 mg/kg tds

Start gradually — once daily day 1, bd day 2, tds day 3

Limit continuous infusion to 0.20 mg/kg/h to 36 hours’ duration in children ketamine. The analgesic action in subanaesthetic doses was first studied by Domino in 1965 [21, 63]. The sites of analgesic action are likely to be located at both spinal and supraspinal levels. In animal models, ketamine blocks higher centres such as the nucleus reticularis gigantocellularis and suppresses activity of laminae I and V in the spinal cord [5, 46]. The dorsal horn is the site of termination of the primary afferents. The NMDA antagonist properties of ketamine may attenuate the “wind up” and central sensitisation phenomenon, and reduce areas of postoperative secondary hyperalgesia [17, 22, 70]. Morphine tolerance is due to a central hyperactive state resulting from neuronal plastic change within the spinal cord and plays a critical role in hyperalgesia associated with nerve damage and inflammation. Such changes involve EAA mediated intracellular cascades, including translocation of phosphokinase C and nitric oxide production. Similar EAA receptor mediated mechanisms are involved with morphine tolerance in the superficial laminae of the spinal cord. Ketamine has been found to attenuate and reverse morphine tolerance in rats. Dextromethorphan and ketamine have been shown to reduce abstinence symptoms in opioid addicts. The S(+) and R(-) stereoisomers of ketamine show differences in action. The S(+) isomer is more potent and cleared faster than R(-) and smaller doses can be used. Faster recovery of cognitive performance occurs with S(+). Haemodynamic and endocrine changes do not differ significantly.

Pharmaceutical preparations Ketamine hydrochloride (Ketalar) is formulated for clinical use as an injection containing 10 mg/ml, 50 mg/ml and 100 mg/ml. Side effects Critically ill patients with catecholamine depletion may respond to ketamine with an unexpected reduction in blood pressure and cardiac output. Emergence reactions (dreams, hallucinations, confusion) are more common with adults, high doses and rapid administration, and are reduced by premedication with benzodiazepines. Cardiovascular effects (hypertension, arrhythmias, sympathetic effect) are less common with the subanaesthetic doses used in chronic pain. There is report of renewed interest in ketamine with abuse at “rave” parties. The source of the drug is often hospital and veterinary supplies. The drug obviously needs to be kept secure in the hospital setting

Indications in chronic pain conditions Patients with pain conditions which have nociceptive and/or neuropathic mechanisms may benefit from ketamine. There has been a significant number of case reports of the analgesic action of long-term ketamine used in postherpetic neuralgia (IV, IM, SC and oral), post-amputation pain, postsurgical neuropathic pain and other neuropathic conditions.

Evidence-based literature Hocking reviewed the literature on ketamine from 1966 through August 2002 and suggested a comprehensive treatment approach with the drug [38]. He proposed performing a fully monitored, placebo controlled intravenous infusion trial of ketamine to assess therapeutic benefit. An intravenous dose of 0.25–0.5 mg/kg is given slowly over 30 minutes with pain assessments before and after administration. If the patient is considered a positive responder, then oral ketamine should be commenced at 0.5 mg/kg taken immediately before going to bed to minimise the likelihood of side effects (level IV). He suggested increasing the dose by 0.5 mg/kg as tolerated until pain relief is obtained or intolerable side effects occur (level IV). The mean effective dose from the literature is 200 mg/day (level II).

398 Anne Miu Han CHAN

Overall, the magnitude of reported benefit from ketamine in chronic pain is often little more than what might be expected by a placebo effect. Unless there is great interest in performing good quality studies in this area, ketamine will remain a thirdline drug that is administered on the basis of weak evidence in patients who have failed to respond to routine pharmacotherapy [38].

Systemic Local Anaesthetic Type Drugs Both lignocaine and mexiletine are local anaesthetic class 1B antiarrhythmic agents. The local anaesthetic type drug stabilises the neuronal membrane by inhibiting the sodium flux required for the initiation and conduction of impulses.

Pharmacology Mechanisms of action It seems that the analgesic mechanism of systemic lignocaine in peripheral nervous system injury is through suppression of ectopic impulse generators in the damaged peripheral nerve [28]. This is achieved by the blocking of sodium channels. Side effects Adverse effects are usually minor, such as light-headedness, somnolence, nausea and perioral numbness. Serious central nervous and cardiovascular side effects are uncommon with the usual therapeutic doses. However, the therapeutic index is narrow for this group of drugs.

Indications Systemic local anaesthetic drugs have been used in peripheral nerve injury, trigeminal neuralgia, diabetic neuropathy and postherpetic neuralgia. Other reported uses include fibromyalgia, migraine and cancer related pain, although the effectiveness for the latter indications was inconsistent

Evidence-based material The best documented effective dose of intravenous lignocaine was 5 mg/kg, which was well tolerated when infused over 30 minutes. Mexiletine (225– 750 mg) caused minor adverse effects that were dose related. Tocainide should not be used because of its toxicity.

Local anaesthetic type drugs are effective in pain due to peripheral nerve injury, but there is little or no evidence to support their use in migraine or cancer related pain [50].

Corticosteroids Corticosteroids may have a role in the treatment of bone pain due to metastatic bone disease [72], in cerebral oedema due to either primary or metastatic tumour [77] and in epidural cord compression [33]. Dexamethasone tends to be the most frequently used corticosteroid because of its high potency, long duration of action and minimal mineralocorticoid effects [14].

Pharmacology Mechanisms of action Corticosteroids may produce analgesia by a variety of mechanisms, including anti- inflammatory effects and reduction of tumour oedema, and potentially by a reduction of spontaneous discharge in injured nerves [76]. Side effects Principal adverse reactions involve multiple organs. Adverse effects are uncommon after a short duration of treatment; risks increase with increased dose and prolonged use. The side effects of steroids are shown in Table 24.01.

Indications Steroids have been used in the treatment of refractory bone pain, cerebral oedema and epidural cord compression. They have also been used in the treatment of aching, burning, lancinating neuropathic pain, severe migraine headache, and pain cause by malignant lesions of the brachial and lumbosacral plexus. There has been some use in the treatment of myofascial pain with trigger points [53]. The use of epidural steroids is covered in Chapter 25 on interventional procedures for pain.

Cannabinoids Cannabinoid receptors are present in the central and peripheral nervous systems, although the

Other Medications and Adjuvants in Pain Management 399

function of these receptors and the endogenous ligands may yet be unclear [10]. It is well known that cannabinoids have analgesic action and that they are also effective antiemetic agents. In animal studies, cannabinoids have been shown to reduce the hyperalgesia and allodynia associated with formalin, capsaicin, carrageenan, nerve injury and visceral persistent pain. The use of cannabinoids has been explored in pain syndromes which are poorly managed.

Pharmacology Side effects The adverse psychological effects of cannabinoids include psychomotor and cognitive impairment; anxiety and panic attacks; and acute psychosis and paranoia. Other adverse effects include dry mouth, blurred vision, palpitations, tachycardia, and postural hypotension. Cardiovascular effects are generally mild and well tolerated.

Indications Evidence-based material A qualitative systematic review by Campbell et al. concluded that cannabinoids are no more effective than codeine in controlling pain [10]. They also have depressant effects on the CNS, which limit their use. Their widespread introduction into clinical practice for pain management is therefore undesirable. Before cannabinoids can be considered for treating spasticity and neuropathic pain, further valid randomised controlled studies are needed.

The alpha-2-adrenoreceptor agonists have analgesic properties when given parenterally, epidurally or intrathecally. Descending noradrenergic antinociceptive systems originating in the brainstem contribute to pain control by suppressing the spinal centripetal transmission of nociceptive impulses. These pathways are activated by stimulation of the locus coeruleus and dorsal raphe nucleus, and analgesia may be mediated by noradrenaline release. An alpha-2 A receptor subtype has been identified in the substantia gelatinosa of the dorsal horn of the spinal cord. Stimulation of these alpha-2 receptors by intrathecal noradrenaline or specific agonists inhibits the firing of nociceptive neurons stimulated by peripheral A-delta and C fibres. Also, intrathecal noradrenaline inhibits the release of substance P by primary afferents of the dorsal horn and suppresses the activity of wide dynamic range neurons evoked by noxious stimulation. There is evidence which has suggested that the antinociception produced by alpha-2-adrenoreceptor agonists may be due to acetycholine release in the spinal cord. It has been suggested that the spinal cord is the major site of analgesic action of alpha-2-adrenoreceptor agonists, and the epidural and intrathecal routes have been considered preferable to the intravenous route [44].

Pharmaceutical preparations Clonidine hydrochloride is available in the form of tablets (Catapres) of 0.1 mg, 0.2 mg and 0.3 mg; as a transdermal therapeutic system (Catapres-TTS) providing continuous systemic delivery of 0.1 mg, 0.2 mg and 0.3 mg over 24 hours; and an epidural injection (Duraclon) containing 100 mcg/ml.

Clonidine Clonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity.

Pharmacology Mechanisms of action Clonidine is a selective agonist at the alpha-2adrenoceptor receptors with a ratio of 200:1 (α2: α1). It inhibits central sympathetic outflow through activation of alpha-2-adrenergic receptors in the medullary vasomotor centre. Clonidine is not a pure alpha-2-adrenoceptor agonist. It also acts on the nonadrenergic imidazoline receptors [44].

Side effects The onset of cardiovascular side effects such as hypotension and bradycardia is slow (30–60 minutes with oral medication) and needs careful monitoring. The CNS side effect of sedation is common. Sudden cessation of clonidine may result in rebound hypertension, nervousness, agitation and tremor.

Indications Clonidine is used in neuropathic pain, for supplemental relief of pain and muscle spasm in fibromyalgia and in cancer pain. It is also used in migraine prophylaxis

400 Anne Miu Han CHAN

Bisphosphonates Bisphosphonates have inhibitory activity on bone resorption and on inflammatory processes. They have proved useful in a series of clinical conditions such as tumour-induced hypercalcaemia, Paget’s disease, osteoporosis and metastatic bone disease.

Pharmacology Mechanisms of action Since accelerated osteolysis and inflammatory response are critical in the development of bone pain, bisphosphonates may have an effect on bone pain by inhibiting the osteoclast process and exerting a possible anti-inflammatory effect [27]. Pharmaceutical preparations The bisphosphonates differ from one and other by the substitution of active side chains on the carbon atom of the base central nucleus of the phosphorous-carbon-phosphorous atoms (P-C-P) [23]. Some examples of bisphosphonates are: 1. First generation: clodronate, etidronate 2. Second generation: pamidronate, tiludronate 3. Third generation: ibandronate, zoledronate. Side effects Toxicity with long-term administration is uncommon. Particular attention must be taken in patients with widespread bone metastases where there is rapid initial osteoblastic response; bisphosphonates may cause symptomatic hypocalcaemia.

Indications Pamidronate and clodronate are used in the treatment of hypercalcaemia of malignancy; treatment of osteolytic bone metastasis of breast cancer and osteolytic bone lesions of multiple myeloma; slowing of bone disease progression; and reduction of tumour-associated metastatic bone pain.

Topical Capsaicin Pharmacology Mechanisms of action Capsaicin, the compound in chili peppers that makes them taste “hot”, binds to nociceptors

in the skin, causing an initial excitation of the neurons and a period of enhanced sensitivity. These changes include itching, pricking, or burning with cutaneous vasodilation, and are thought to be due to selective stimulation of afferent C fibres and release of substance P. This is followed by a refractory period with reduced sensitivity and after repeated applications, persistent desensitisation, possibly due to depletion of substance P [52].

Pharmaceutical preparations Topical capsaicin is available as a 0.025% cream (Zostrix) in tubes of 0.7 oz, 1.5 oz and 3 oz; and as a 0.075% cream (Zostrix HP) in tubes of 1 oz and 2 oz. Side effects The adverse effects are mainly at the application site (burning, stinging, erythema) and systemic events are rare [60]. Respiratory irritation has been reported from inhalation of dried cream [58].

Indications Topical creams with capsaicin are used to treat pain from postherpetic neuralgia and diabetic neuropathy, osteoarthritis and rheumatoid arthritis [6, 60]. Capsaicin has also been used to treat pain due to pruritis, psoriasis, mastectomy, bladder disorders and cluster headaches [60].

Evidence-based material Topical capsaicin is better than placebo for the treatment of chronic pain in neuropathic and musculoskeletal disorders [50, 79]. Mason et al. in their systematic review calculated the number needed to treat (NNT) for the studied conditions [50]. The NNT using topical capsaicin 0.075% was 5.7 for neuropathic conditions and 6.4musculoskeletal conditions. These NNT results were lower compared with those calculated from the Zhang 1994 meta-analysis [79].

Other Drugs — Antihistamines The current literature supports the direct analgesic effects of various antihistaminic agents. The specific antihistamines identified are hydroxyzine, orphenadrine and diphenhydramine [62, 68].

Other Medications and Adjuvants in Pain Management 401

Indications Despite evidence of analgesic effects in single-dose studies of various antihistamines, clinical experience has failed to confirm significant analgesic utility from this class of drugs [31]. The use of these agents is associated with potential side effects, including

sedation and dry mouth. These drugs should only be considered in patients who have a primary indication other than pain. A trial of hydroxyzine, for example, is sometimes used in cancer patients where pain is complicated by anxiety, nausea or itching [12].

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

16. 17. 18. 19. 20. 21. 22. 23.

Adams RD, Victor M. Headache and other craniofacial pains. In Adams RD, Victor M, eds. Principles of Neurology, 4th edn. New York: McGraw-Hill, 1989:134–54. Akers J. The renaissance of ketamine. Australas Anaesth 2000;25–35. Arezzo JC. Possible mechanisms for the effects of botulinum toxin on pain. Clin J Pain 2002;18(6 Suppl):S125–32. Atkinson JH, Ancoli-Israel S, Slater MA, et al. Subjective sleep disturbance in chronic back pain. Clin J Pain 1988;4:225– 32. Bowdle TA, Horita A, Kharasch ED. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone, 1994:337–92. British Medical Association. Royal Pharmaceutical Society of Great Britain. British National Formulary. London: BMA, RPS, 2003 (No. 45). Bruera E, Roca E, Cedaro L, et al. Action of oral methylprednisolone in terminal cancer patients: A prospective, randomized, double-blind controlled study. Cancer Treat Rep 1985;(69):751–4. Bruera E, Chadwick S, Brenneis C, et al. Methylphenidate associated with narcotics for the treatment of cancer pain. Cancer Treat Rep 1987;(71):67–70. Butcher SP, Liptrot J, Aburthnott GW. Characterization of methylphenidate and nomifensine induced dopamine release in rat striatum using in vivo brain microdialysis. Neurosci Lett 1991;122:245–8. Campbell FA, Tramer MR, Carroll D, et al. Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review. BMJ 2001;323(7303):13–6. Challman TM. Lipsky JL. Methylphenidate: Its pharmacology and uses. Mayo Clin Proc 2000;75:711–21. Cherny NI, Portenoy RK. Practical issues in the management of cancer pain. In Wall PD, Melzack R, eds. Textbook of Pain, 4th edn. London: Churchill Livingston, 1999:1498. Collingridge GL, Singer W. Excitatory amino acid receptors and synaptic plasticity. Trends Pharmacol Sci 1990;1:290– 6. Collins J. Pain management and pediatric palliative care. In Justins DM, ed. Pain 2005 — An Updated Review: Refresher Course Syllabus. Seattle: IASP Press, 2005. Committee on the Review of Medicine 1980. Systematic review of the benzodizepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, trazolam, nitrazepam and flurazepam. BMJ 1980;280:910–2. Court JE, Kase CS. Treatment of tic douloureux with a new anticonvulsant (clonazepam). J Neurol Neurosurg Psychiat 1976;39:297–9. Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and Pain Management, 3rd edn. Philadelphia: Lippincott-Raven Publishers, 1998:675–99. Dejgard A, Petersen P, Kastrup J. Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet 1988:1(85758576):9–11. Dellemijn PL, Fields HL. Do benzodiazepines have a role in chronic pain management? Pain 1994;57:137–52. Devor M, Gorvin-Lippmann R, Raber P. Corticosteroids suppress ectopic neural discharge originating in experimental neuromas. Pain 1985;22:127–37. Domino EF, Chidiff P, Corssen G. Pharmacologic effects of CI-581, a new dissociative anesthetic in humans. Clin Pharmacol Ther 1965;6:279–91. Eide PK, Stubhaug A, Oye I. The NMDA antagonist ketamine for prevention and treatment of acute and chronic post op pain. Balliere Clin Anaes 1995;9:539–53. Fleisch H. Biphosphonates: Pharmacology and use in the treatment of tumour-induced hypercalcemic and metastatic bone disease. Drugs 1991;42:919–44.

402 Anne Miu Han CHAN

24. Forest WH, Brown BW, Brown CR, et al. Dextroamphetamine with morphine for the treatment of postoperative pain. N Engl J Med 1977;296:712–5. 25. Fromm GH, Terence CF, Chatta AS. Baclofen in the treatment of trigeminal neuralgia: Double blind study and long term follow up. Ann Neurol 1984;(25):240–7. 26. Fromm GH. Baclofen as adjuvant analgesic. J Pain Symptom Manage 1994;9(8):500–9. 27. Fulfaro F, Casuccio A, Ticozzi C, et al. The role of biphosphonates in the treatment of painful metastatic bone disease: A review of phase III trials. Pain 1998;78:157–69. 28. Galer BS, Miller KV, Rowbotham MC. Response to intravenous lidocaine infusion differs based on clinical diagnosis and site of nervous system injury. Neurology 1993;(43):1233–5. 29. Gear RW, Levine JD, Gordon NC, et al. Benzodiazepine mediated antagonism of opioid analgesia. Pain 1997;71:25– 9. 30. Gehling M, Tryba M. New aspects of ketamine in post op pain management. Acute Pain 1998;1:22–34. 31. Glazier HS. Potentiation of pain relief with hydroxyzine: A therapeutic myth? Drug Intell Clin Pharm 1990;24(5):484– 8. 32. Gobel H. Botulinum toxin in migraine prophylaxis. J Neurol 2004;251(Suppl 1):8–11. 33. Greenberg HS, Kim J, Posner JB. Epidural cord compression from metastatic tumor: Results with a new treatment protocol. Ann Neurol 1980;8:361–6. 34. Hamlin C, Gold MS. Anxiolytics: Predicting response/maximizing efficacy. In Gold MS, Lydiard RB, Carman JS, eds. Advances in Psychopharmacology: Predicting and Improving Treatment Response. Boca Raton: CRC Press, 1984:22576. 35. Harris JA, Westbrook RF. Effects of benzodiazepine microinjection into the amygala or periaqueductal gray on the expression of conditioned fear and hypoalgesia in rats. Behav Neurosci 1995;109:295–304. 36. Herman RM, Luzansky SCD, Ippolito R. Intrathecal baclofen suppresses central pain in patients with spinal lesions. Clin J Pain 1992;8:338–45. 37. Hirota K, Lambert DG. Ketamine: Its mechanisms of action and unusual clinical uses. Br J Anaesth 1996;77:441–4. 38. Hocking G, Cousins MJ. Ketamine in chronic pain management: An evidence-based review. Anesth Analg 2003;97(6):1730–9. 39. Hollister LE. Long term use of diazepam. JAMA 1981;246:1568–70. 40. Hurd L, Ungerstedt U. In vivo neurochemical profile of dopamine uptake inhibitors and releasers in rat caudateputamen. Eur J Pharmacol 1989;166:251–60. 41. Ivy AC, Goetzl FR, Burrill DY. Morphine-dextroamphetamine analgesia with morphine for the treatment of postoperative pain. N Engl J Med 1977;296:712–5. 42. Jankovic J, Hallett M, eds. Therapy with Botulinum Toxin. New York: Marcel Dekker Inc., 1994. 43. Janowsky A, Schweri MM, Berger P, et al. The effects of surgical and chemical lesions of striatal (3H)threo-(+/-)methylphenidate binding: Correlation with (3H)dopamine uptake. Eur J Pharmacol 1985;108:187–91. 44. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists: Their pharmacology and therapeutic role. Anaesthesia 1999;54(2):146–65. 45. King SA, Strain JJ. Benzodiazepine use by chronic pain patients. Clin J Pain 1990a;6:143–7. 46. King SA, Strain JJ. Benzodiazepine and chronic pain. Pain 1990b;41:3–4. 47. Kohrs R, Durieux MS. Ketamine: Teaching an old drug new tricks. Anesth Analg 1998;87:1186–93. 48. Luger TJ, Hayashi T, Grabner-Weiss C, et al. Effects of the NMDA-antagonist, MK801, on benzodiazepine-opioid interactions at the spinal and supraspinal level in rats. Br J Pharmacol 1995;114:1097–103. 49. Marks J. The benzodiazepines — Use and abuse. Arzneimittel Forschung/Drug Research 1980;30(I)(5a):889–91. 50. Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 2004:328(7446):991. 51. Moriyoshi K, Masu M, Ishii T, et al. Ketamine protects hippocampal neurons from anoxia in vitro. Neuroscience 1987;2:673. 52. Nolano M, Simone DA, Wendelschafer-Crabb G, et al. Topical capsaicin in humans: Parallel loss of epidermal nerve fibres and pain sensation. Pain 1999;81:135–45. 53. Omoigui S. Pain Drugs Handbook, 2nd edn. Boston: Blackwell Science, 1999. 54. Pick CG. Strain differences in mice antonociception: Relationship between alprazolam and opioids. Eur Neuropsychopharmacol 1996;6:201–5. 55. Pick CG. Antinociceptive interaction between alprazolam and opioids. Brain Res Bull 1997;42:239–43. 56. Pilowsky I, Chapman CR, Bonica JJ. Pain depression and illness behavior in a pain clinic population. Pain 1977;4:183– 92. 57. Racz GB. Botulinum toxin as a new approach for refractory pain syndromes. Pain Digest 1998;8:353–6. 58. Rains C, Bryson HM. Topical capsaicin. A review of its pharmacological properties and therapeutic potential in postherpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging 1995;7:317–28.

Other Medications and Adjuvants in Pain Management 403

59. Raj PP. Botulinum toxin therapy in pain management. Anesthesiol Clin N Am 2003;21(4):715–31. 60. Reynolds JEF, ed. Martindale: The Extra Pharmacopoeia, 32nd edn. London: Royal Pharmaceutical Society, 1999. 61. Rozans M, Dreisbach A, Lertora JJ, et al. Palliative uses of methylphenidate in patients with cancer: A review. J Clin Oncol 2002;20(1):335–9. 62. Rumore MM, Schlichting DA. Clinical efficacy of antihistamines as analgesics. Pain 1986;25:7–22. 63. Sadove MS, Shulman M, Hatano S, et al. Analgesic effects of ketamine in subdissociative doses. Anesth Analg 1971;50:452–7. 64. Schantz EJ, Johnson EA. Preparation and characterization of botulinum toxin type A for human treatment. In Jankovic J, Hallett M, eds. Therapy with Botulinum Toxin. New York: Marcel Dekker Inc., 1995:41–9. 65. Schweri MM, Skolnick P, Rafferty MF, et al. (3H)Threo-(+/-)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in the corpus striatum: Correlation with the stimulant properties ritalinic acid esters. J Neurochem 1985;45:1062–70. 66. Sellin LC, Theless S, Dasgupta BR. Different effects of types A and B botulinum toxin on transmitter release at the rat neuromuscular junction. Acta Physiol Scand 1983;119(2):127–33. 67. Snyder S, Enna JJ, Young AB. Brain mechanisms associated with the therapeutic actions of benzodiazepines: Focus on neurotransmitters. Am J Psychiat 1977;134:662–4. 68. Stambaugh JE, Lance C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest 1983;(Suppl 1):111–7. 69. Strichartz G. Protracted relief of experimental neuropathic pain by systemic local anesthetics: How, where, and when. Anesthesiology 1995;83(4):654–5. 70. Stubhaug A, Breivik H, Kristian P, et al. Ketamine reduces postoperative hyperalgesia. Prog Pain Res Manage 1997;8:333– 49. 71. Sugiyama H. Clostridium botulinum neurotoxin. Microbiol Rev 1980;44:419–48. 72. Tannock I, Gospodarwicz M, Meaki W, et al. Treatment of metastatic prostatic cancer with low dose prednisone: Evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol 1989;7(5):590–7. 73. Tsui JKC, Bhatt M, Calne S, et al. Botulinum toxin in the treatment of writer’s cramp: A double blind study. Neurology 1993;43:183–5. 74. Van Tulder MW, Touray T, Furlan AD, et al. for Cochrane Back Review Group. Muscle relaxants for nonspecific low back pain: A systematic review within the framework of the Cochrane Collaboration. Spine 2003;28(17):1978–92. 75. Wall SC, Gu H, Rudnick G. Biogenic amine flux mediated by clonal transporters stably expressed in culture cell lines: Amphetamine specificity for inhibition and efflux. Mol Pharmacol 1995;45:544–50. 76. Watanabe S, Bruera E. Corticosteroids as adjuvant analgesics. J Pain Symptom Manage 1994;9:442–5. 77. Weinstein JD, Toy FJ, Jaffe ME, et al. The effect of dexamethasone on brain edema in patients with metastatic brain tumor. Neurology 1973;23:121–9. 78. Wüster M, Duka T, Herz A. Diazepam effects on striatal metenkephalin levels following long-term pharmacological manipulation. Neuropharmacology 1980;19:501–5. 79. Zhang WY, Li Wan Po A. The effectiveness of topically applied capsaicin. A meta-analysis. Eur J Clin Pharmcol 1994;46:517–22.

25

Steven H. S. WONG

Interventional Procedures in Pain Management: An Overview

Introduction

INTRODUCTION AIDS TO ENHANCE PRECISION OF INTERVENTIONAL PROCEDURES MEANS OF NEURAL BLOCKADE IN INTERVENTIONAL PROCEDURES Chemical agents Physical means COMMON INTERVENTIONAL PROCEDURES IN PAIN MANAGEMENT AND THEIR EFFECTIVENESS Injection at peripheral sources of pain Nerve block Sympathetic block Injections for chronic back pain Implantable devices AN ALGORITHMIC APPROACH CONCLUSION REFERENCES

Interventional procedures for pain management range from local injections to specific neural blockade of the sensory supply to specific body structures. These procedures have been performed by different medical specialists including the orthopaedic surgeons, neurosurgeons and anaesthetists. While they are usually effective in the short term, the efficacies of these interventional procedures in the treatment of chronic pain syndromes have been questioned by a number of recent evidence-based systematic reviews. In recent decades, with the introduction and acceptance of the bio-psycho-social model of chronic pain, multidisciplinary pain management clinics have become very popular. These clinics have input from practitioners from multiple medical specialties including anaesthetists, orthopaedic surgeons, neurologists, neurosurgeons, psychiatrists, clinical oncologists and rehabilitative physicians, as well as different allied health discipline personnel such as physiotherapists, occupational therapists and clinical psychologists. A number of evidencebased practice guidelines have been developed to enhance the efficacy of interventional procedures. It is recommended that interventional procedures should be performed with an algorithmic approach and in accordance with a multidisciplinary treatment plan. This chapter presents a general overview of interventional procedures in the management of pain. An account of various means to aid accurate placement of needles or devices will be given and some selected common interventional procedures will be briefly described. The efficacy, limitations and risks of interventional procedures will be discussed with reference to recent evidence. Lastly, an algorithmic approach in the clinical practice of interventional procedures will be described. For more detailed discussion on some important interventional

406 Steven H. S. WONG

procedures, please refer to Chapters 11 and 26 to 31 of this textbook.

Aids to Enhance Precision of Interventional Procedures Fluoroscopy The use of portable X-ray machines with fluoroscopy has revolutionised the practice of interventional procedures. It allows instantaneous production of the radiological image by the image intensifier and viewing on the monitoring screen. Fluoroscopy is most useful in procedures around the spine where great precision is required to avoid injury to the spinal cord. The use of radiographic contrast agents allows direct visualisation and estimation of the spread of therapeutic agents, which is especially important in neurolytic blockade. Special precautions should be undertaken in performing interventional procedures under fluoroscopic guidance. It is important to comply with the radiation safety ordinance to prevent inadvertent radiation exposure to the patient as well as the staff [11]. The use of radiographic contrast media also requires caution because of their adverse effects; specific enquiry into patients’ allergic history is advised and steroid cover may be required [49].

Computerised tomography Computerised tomography produces crosssectional views of the body. It has been employed in interventional procedures involving deeply seated structures such as the coeliac plexus in the management of pain in carcinoma of the pancreas. Despite its higher precision, the technique has not gained much popularity because it is very tedious, requiring movement of the operator between the examination room and the control room for every radiological exposure after adjustment of the needle.

Ultrasound The availability of compact portable ultrasound equipment has recently made the ultrasound machine a very popular device among anaesthetists in the performance of regional blockade [27].

Ultrasound also has the advantage of being free from radiation hazard. It is especially useful for locating nerves among other soft tissues, such as the brachial plexus and peripheral nerves of the limbs. However, it is not as useful in nerve blockade around bony structures such as the spine. The efficacy of ultrasound-guided nerve blockade is also highly dependent on the skills of the operator.

Nerve stimulators The nerve stimulator is useful in localisation of nerves in performing neural blockade. Sensory and motor nerves can be differentiated by varying the frequency of stimulation, with 50–100 Hz producing paraesthesia while 1–2 Hz produces visible muscle twitching. The proximity of the needle to the nerve can be assessed by the minimum amplitude of current required for stimulation, and amplitudes of less than 0.3 mV usually suggest optimal positioning of the needle. The nerve stimulator is routinely employed in the radiofrequency thermocoagulation technique. It is important that local anaesthetics should not be given via the needle until accurate positioning of the needle has been confirmed, as even a tiny volume of local anaesthetic will completely block off the stimulation response and obviate subsequent use of the technique.

Means of Neural Blockade in Interventional Procedures Neural blockade can be achieved by using chemical agents such as local anaesthetics or neurolytic agents, or the use of physical means such as cold or heat.

Chemical agents The choice of chemical agents for neural blockade depends on whether the procedure is diagnostic or therapeutic. Local anaesthetics are used for both diagnostic and therapeutic procedures. Neurolytic agents may be considered for therapeutic procedures in selected patients. Novel agents, such as botulinum toxin and ziconotide, have been employed to block pain transmission in interventional procedures for a much longer duration than local anaesthetics provide.

Interventional Procedures in Pain Management: An Overview 407

Local anaesthetics The most commonly used local anaesthetics are the amide group derivatives. They differ in their onset time and duration of action. Lignocaine has the fastest onset time of about 10 to 20 minutes and the shortest duration of action of about 1 to 2 hours if given for peripheral nerve blockade. Bupivacaine has a slower onset time of about half an hour and a longer duration of action of about 4 to 5 hours. The most serious risk with the use of local anaesthetics is systemic toxicity if injected into the circulation inadvertently and results in convulsion, arrhythmias and cardiac arrest. Bupivacaine has the highest cardiotoxicity and it is often irreversible while ropivacaine has less cardiotoxicity. Precautions should be taken to prevent intravascular injection and not to exceed the recommended dose limit. In patients with chronic pain, the effect of neural blockade using local anaesthetics may sometimes outlast the duration of the local anaesthetic itself. It is more commonly seen with sympathetic blockade in complex regional pain syndrome. Therefore, repeated sympathetic blockade with local anaesthetics is recommended in this group of patients when appropriate.

Neurolytic agents Alcohol (ethanol) and phenol are the two most commonly used neurolytic agents. They have similar mechanism of action and cause destruction to neural tissues resulting in axonal degeneration and Wallerian degeneration. In addition, phenol has high affinity for vascular tissues and injection of a large volume in highly vascular areas such as the coeliac plexus is not recommended. The use of neurolytic blockade is reserved for management of cancer pain patients with limited life expectancy. This is because the duration of effect usually lasts 3 to 6 months and pain tends to recur with regeneration of nerve fibres. Also, there is a possibility of development of deafferentation pain after somatic nerve injury. Phenol is available as a 10% solution in a mixture with X-ray contrast media, such as iothalamate meglumine (Conray). Alcohol is available as an absolute 100% solution and is often diluted to a 50–75% solution with bupivacaine.

Botulinum toxin Botulinum toxin is the most potent biological toxin produced by the bacterium Clostridium botulinum. It inhibits the release of acetylcholine at the neuromuscular junction, thereby causing muscle paralysis. Newer studies show that it may also have a direct analgesic action. Postulated mechanisms include inhibition of release of substance P, glutamate and other peptides and neurotransmitters from nociceptors, suppression of neurogenic inflammation and reduction of sympathetic activity [29].

Ziconotide Ziconotide is the synthetic equivalent of the basic peptide present in the venom of a marine snail. It produces potent antinociceptive effects by selectively binding to the N-type voltage-sensitive calcium channels, thereby blocking neurotransmission from primary nociceptive afferents. Intrathecal ziconotide has been demonstrated to have a place in the treatment of patients with severe chronic pain who are intolerant of or refractory to other analgesic therapies [37].

Physical means Various physical means to produce destruction of neural tissues have been employed in the management of chronic pain. These include cryotherapy and radiofrequency treatment.

Cryotherapy Cryotherapy produces destruction of neural tissue by freezing it with the tip of a cryoprobe which is cooled by rapid expansion of a gas passed inside it. The tip of the probe can reach as low a temperature as -60˚C with carbon dioxide, or -70˚C with nitrous oxide. The cryoprobe is inserted to the target site under fluoroscopic guidance. Cryotherapy is gradually losing its position to radiofrequency treatment as the physical means of neural destruction. Disadvantages of cryotherapy include the bulkiness of the cryoprobe in comparison with the radiofrequency electrode, and the subsequent need for larger doses of local anaesthetics during placement, which interferes with the use of the nerve stimulator.

408 Steven H. S. WONG

Radiofrequency treatment Conventional radiofrequency treatment produces a heating effect on the nerve by passing a radiofrequency current through a circuit which consists of an active electrode, a ground electrode and the radiofrequency generator. The active electrode has an insulated body and a noninsulated tip which is available in various lengths. It is inserted to the target site under fluoroscopic guidance. The ground electrode is a gel pad which is applied on the patient’s body. The two electrodes are connected to a radiofrequency generator which delivers a radiofrequency current at a frequency of 460 kHz [46, 55]. When the circuit is completed, a high current density generated at the tip of the active electrode will heat up the surrounding tissues. The temperature at the tip of the electrode is constantly measured by a thermocouple. By selecting the appropriate length of non-insulated tip and adjusting the amplitude and the duration of the current, a controlled thermal lesion can be produced. With conventional continuous radiofrequency current, the tissue is heated to a temperature of 60–70˚C for a period of about 60 seconds. Irreversible nerve damage due to coagulation of tissue proteins will occur at temperatures of above 60˚C. A new technique of radiofrequency treatment has recently been developed. It delivers pulses of highvoltage radiofrequency current to the nerve without heating it to a degree at which tissue coagulates, as the heat generated is dissipated between pulses. The apparent lack of nerve damage is advantageous in the lesioning of somatic nerves, which have a higher chance of developing deafferentation pain [1]. The mechanism of action of pulsed radiofrequency is still not clear. It is postulated that the electric field, rather than the temperature, induces changes in the neuron and produces a neuromodulatory effect [14].

Common Interventional Procedures in Pain Management and Their Effectiveness A wide variety of interventional procedures are practised in pain management. They can be

classified according to their sites and mechanisms of action. Some common interventional procedures in pain management are outlined below. Despite the enthusiasm and the wide acceptance of interventional procedures in the management of chronic pain, high level research-based evidence is still lacking in the support of their practice. There have been few high quality randomised controlled studies on the effectiveness of interventional procedures. Some recent systematic reviews have examined the effectiveness of various interventional procedures, but contradictory results were found regarding their efficacy. Brief discussions on the efficacy will be given for individual procedures.

Injection at peripheral sources of pain These include simple injection techniques like trigger point injection and injection over inflamed tendons or fasciae for treatment of conditions like tennis elbow or plantar fasciitis. The injectate used is usually a local anaesthetic and may have in addition a depot corticosteroid preparation. Local anaesthetics produce a transient effect through blocking of neural transmission while corticosteroids exert a more long-lasting effect by their anti-inflammatory actions. Recently, botulinum toxin has been used in the treatment of various disorders associated with painful muscle spasms with a much longer duration of action than local anaesthetics.

Trigger point injection Trigger points are discrete, focal, hyperirritable spots located in taut bands of skeletal muscle. They are mostly found in muscles that maintain body posture, such as those in the paraspinal and girdle regions. The trigger points are tender on palpation and may cause a specific referred pain pattern. The cause is unclear but is postulated to be related to repetitive microtrauma of muscle fibres. It is more common in middle-aged females and is usually associated with anxiety states. The diagnosis is often myofascial pain syndrome or fibromyalgia [2]. Trigger point injection should be performed in conjunction with relaxation and stretch exercises, as well as psychological therapy if indicated. The trigger points are injected in a fanwise fashion using a small gauge hypodermic needle with a

Interventional Procedures in Pain Management: An Overview 409

small amount of local anaesthetic. A series of three to four injections over a period of 1 to 2 months may be effective in abolishing the trigger points with marked relief of pain. The operator should note the total amount of local anaesthetic to be injected in patients with multiple trigger points, to avoid overdose toxicity. A randomised double-blind crossover trial comparing trigger point injections using local anaesthetic with normal saline (n = 15) has shown that both techniques resulted in significant reduction in pain even up to 7 days after treatment [13]. In another double-blind study comparing trigger point injections using local anaesthetic (n = 13) with dry needle (n = 20), it was found that dry needle was more effective than injection with local anaesthetic [12]. A systematic review pooling the results of these and some other studies concluded that trigger point injection was no more effective than placebo injection [30]. It is now believed that the mechanism of action of trigger point injections in the treatment of myofascial pain syndrome is the release of contraction in the contractile units of the myofibrils by the insertion of the needle rather than the local anaesthetic. It explains why a dry needle works. It would then become very difficult to compare local anaesthetic injection with “placebo” injection, which in fact is an effective treatment.

Injection for tennis elbow Tennis elbow is caused by overuse of the extensor tendons of the forearm. The resulting lateral epicondylitis presents most commonly with localised pain over the bony origin of the tendons of the extensor carpi radialis brevis and less commonly those of the extensor carpi radialis longus. The pain can be effectively treated by injection over the inflamed tendons with depot steroid in a small volume of local anaesthetic. It is important to employ strict aseptic technique and avoid direct injection into the tendons [54]. Injection for plantar fasciitis Plantar fasciitis involves the inflammation of the plantar fascia and is associated with prolonged walking or exercise. The pain can be effectively treated by injecting over the medial aspect of the calcaneus with depot steroid in a small volume of local anaesthetic [54].

Injection for painful muscle spasms Botulinum toxin, originally developed for treatment of dystonia and movement disorders, has been found to be effective for the treatment of a number of chronic pain conditions associated with painful muscle spasms. These include myofascial pain syndrome or fibromyalgia, temporomandibular joint pain and orofacial pain. Botulinum toxin has also been used to treat some headaches associated with muscle contractions such as chronic tension headache and cervicogenic headache [16].

Nerve block Nerve block plays a crucial role in the diagnosis and treatment of pain syndromes. The procedure can be applied to nearly all body structures that have got a nerve supply. Commonly practised nerve blocks include intercostal nerve block for chest wall pain, and injection of the trigeminal nerve and its branches in trigeminal neuralgia or other causes of orofacial pain. Sometimes, the pain in the body structures is a referred pain that has occurred as a result of pathology in the supplying nerve or as a result of entrapment of the supplying nerve by surrounding tissues or fibrosis of scarred tissues. Common examples include intercostal nerve block for entrapment by thoracotomy scars, occipital nerve block for cervicogenic headache as a result of nerve compression or occipital neuralgia, and suprascapular nerve block for shoulder pain caused by nerve entrapment. Accurate placement of needles in somatic nerve block is facilitated by the use of fluoroscopy, or by the use of a peripheral nerve stimulator. In recent years, the availability of ultrasonograpy has allowed clear visualisation of nerves and has popularised the practice of nerve blockade.

Intercostal nerve block Intercostal nerve block is useful in alleviating chest wall pain caused by fracture of ribs, or cancer infiltration of the chest wall. It is also useful when the chest wall pain is a referred pain due to entrapment of the intercostal nerves by thoracotomy scar tissues [10]. The most serious risk of intercostal nerve block is pneumothorax and meticulous care should be exercised during the procedure. A chest radiograph

410 Steven H. S. WONG

needle and allowing visualisation of the extent of the spread of phenol (Fig. 25.01).

Blockade of the trigeminal nerve and its branches The trigeminal nerve branches into three main divisions, namely the ophthalmic, maxillary and mandibular divisions, and supplies the sensory innervation to the upper, middle and lower thirds of the face.

Figure 25.01 Neurolytic intercostal nerve block for a patient with chest pain due to tumour infiltration of the chest wall. Note the spread of contrast along the course of the intercostal nerves.

In the idiopathic type of trigeminal neuralgia, trigeminal ganglion block may be indicated when conventional pharmacological treatment fails to control the pain or if there are intolerable side effects. In the past, neurolytic blocks using glycerol or alcohol have been performed. Nowadays, radiofrequency thermocoagulation has become the method of choice for this procedure (Fig. 25.02) [24]. Please also refer to Chapter 11 for more details.

is often performed after the procedure to exclude any complication. For nerve entrapment, therapeutic block with corticosteroids may be considered. For tumour infiltration, neurolytic block with phenol is commonly performed. The use of fluoroscopy and phenol in contrast enhance the safety of the procedure by facilitating accurate placement of the

There are no randomised controlled trials in the literature on the use of radiofrequency thermocoagulation for the treatment of trigeminal neuralgia. A recent systematic review has attempted to compare the effectiveness of radiofrequency thermocoagulation with other ablative techniques such as glycerol rhyzolysis, balloon microcompression and stereostatic

Figure 25.02

Radiofrequency thermocoagulation of the trigeminal ganglion. Note that the target of insertion of the electrode (A) is the foramen ovale (B).

Interventional Procedures in Pain Management: An Overview 411

radiosurgery. It was concluded that radiofrequency thermocoagulation offers the highest rates of complete pain relief and is associated with the least complications [24]. Blockade of the terminal branches of the trigeminal nerve is useful for relieving pain arising from the face as a result of localised tumour, or to abolish the trigger zones when present in trigeminal neuralgia or postherpetic neuralgia. The terminal branches of the ophthalmic, maxillary and mandibular divisions of the trigeminal nerve can be blocked by local infiltration over the supraocular and supratrochlear nerves, infraorbital nerve and mental nerve respectively [43].

Greater occipital nerve block The greater occipital nerve is derived from the dorsal rami of the C2 nerve. It supplies the sensation to the scalp over the occiput. Along its winding course as it ascends from the posterior neck, the nerve is susceptible to compression by the intermingled layers of muscles that are often in spasm in conditions such as cervical spondylosis. The resulting referred pain to the occipital area is referred to as cervicogenic headache. Other causes of occipital pain include occipital neuralgia and tension headache. Greater occipital nerve block has also been found to be effective as a transitional therapy for cluster headache. The mechanism of action is unclear and may be related to the interference of the trigeminal activity as well as interruption of the trigeminal autonomic reflex pathway [35]. In a double-blind placebo controlled study comparing subocciptial injection of steroid (n = 13) with normal saline (n = 10) in patients with cluster headache, it was found that 85% of the patients in the treatment group became pain-free in the first week after the injection compared to none in the control group and the effect was maintained for up to 4 weeks [3]. Greater occipital nerve block is most easily performed at the superior nuchal line one-third of the distance from the greater occipital protuberance to the mastoid process. The nerve runs immediately medial to the occipital artery.

Suprascapular nerve block The suprascapular nerve is derived from the C5 and C6 nerve roots of the brachial plexus. It supplies the sensation to the shoulder joint as well as the motor function of the supraspinatus and the infraspinatus muscles. Passing underneath the coracoclavicular ligament through the suprascapular notch, the nerve is susceptible to direct trauma or compression by shoulder straps. The referred pain to the shoulder can mimic other causes of shoulder pain. Pain in the shoulder can be relieved by blocking the suprascapular nerve at the suprascapular notch by injection of local anaesthetic with depot steroid [44]. Careful precaution must be taken to protect the shoulder after the injection as the local anaesthetic would temporarily block all the sensation from the shoulder joint. Please also refer to Chapter 26 for more details of this procedure.

Sympathetic block The sympathetic nervous system is the major nerve supply to the visceral organs of our body. It carries vasoconstricting efferents to various organs such as the gut, the kidneys and the skin. It is important in diverting blood flow to vital organs such as the brain and the heart in fright and flight response. It also carries pain afferents from various organs such as the heart, the gastrointestinal and the urogenital tracts. Pain from visceral organs can be interrupted by sympathetic blockade. The classic example is the use of epidural analgesia for labour pain, where a diluted local anaesthetic may block the sympathetic fibres while sparing the sensory and motor fibres and can successfully interrupt the pain afferents from the contracting uterus during the first stage of labour. The sympathetic nervous system forms paired chains of sympathetic ganglia, which run along the anterolateral aspects of the cervical, thoracic and lumbar vertebrae. These sympathetic ganglia receive preganglionic fibres from T1 to L2 levels of the spinal cord and send out postganglion fibres to various organs. These ganglia and the network of pre- and postganglionic fibres form the coeliac plexus and the hypogastric plexus. Selective sympathetic block can be performed at these ganglia and plexuses because they are anatomically

412 Steven H. S. WONG

separated from the somatic nerves. These are discussed in detail in Chapter 27.

Intravenous regional sympathetic block Intravenous regional sympathetic block with guanethidine is a non-invasive alternative to block the sympathetic outflow to the extremities. A diluted solution of guanethidine (10 mg in about 25 ml normal saline for the upper limb and about 40 ml for the lower limb) is injected intravenously into the affected limb with a pneumatic tourniquet on for about 20 minutes. Guanethidine will cause release of noradrenaline and a subsequent depletion of noradrenaline from the sympathetic nerve endings resulting in a prolonged sympathetic block. In patients with sympathetically maintained pain, the noradrenaline release may cause exacerbation of pain, but it is important not to add local anaesthetic in the guanethidine solution as it will inhibit the noradrenaline release [5]. Apart from guanethidine, bretylium is also useful for intravenous regional sympathetic block. There are few randomised controlled studies in the literature on the effectiveness of intravenous regional sympathetic block for treatment of peripheral neuropathic pain. Some of the studies [17, 40] have been criticised for diluting guanethidine in lignocaine thus limiting its usefulness. Nevertheless, a randomised doubleblind crossover study comparing guanethidine in normal saline with normal saline showed that there was no significant difference [15].

Injections for chronic back pain Chronic back pain is the most common health problem that has significant societal and economic impact. Studies have shown that a number of structures in the spine are capable of generating pain. Common ones include the facet joint, the sacroiliac joint, nerve roots and the intervertebral disc. Injection procedures play an important role in the diagnosis and treatment of chronic back pain. They are discussed in detail in Chapter 28. There have been only a few randomised controlled trials on lumbar facet joint injections. In one study comparing a total of 6 ml of local anaesthetic with steroid into two adjoining lumbar facet joints (n = 28) with a total of 8 ml of normal saline into two facet joints (n = 42), it was found that there was no significant difference between the two groups with

respect to subjective assessment, objective disability score and work outcome [23]. Notice that the volume of injectate used was far in excess of what is recommended in current practice, which should not exceed 1 ml into each facet joint. In another study comparing a total of 2 ml of local anaesthetic with steroid into two adjoining lumbar facet joints (n = 49) with an equal volume of normal saline (n = 48), it was found that there was no significant difference in the improvement (42% vs 33%) between the two groups in the flexion of the spine, the functional status and self-report of overall effect within 3 months after injection. Despite the fact that there was a significantly higher percentage of patients with marked improvement at 6 months in the treatment group compared with the control group (42% vs 15%), it was concluded that the results were not significant when the percentage of patients in the treatment group having sustained improvement from the first to the sixth month was compared to that in the control group (22% vs 10%) [7]. There was only one randomised, non-placebo controlled trial concerning cervical facet joint injection. Intra-articular injection of corticosteroid (n = 21) was compared with local anaesthetic (n = 20) in patients with cervical facet joint pain after whiplash injury. It was found that in both groups less than half of the patients reported pain relief for more than 1 week and a conclusion was made that intra-articular steroid injection was not effective [4]. However, it was worth noting that in the study only a single cervical facet joint was injected, which is an uncommon practice as it is very unlikely that whiplash injury involves only a single facet joint. Besides, about one-fifth of the patients in both groups had prolonged pain relief of up to 2 months. Although it was attributed to placebo effect by the author, there was no placebo group in the study design. There have been a few randomised controlled trials on the use of radiofrequency medial branch neurotomy in the treatment of chronic facet joint pain. In one study, a group of patients with lumbar facet joint pain was randomised to receive radiofrequency lesion of medial branches (n = 15) or a sham procedure (n = 16) in which the electrodes were introduced but without radiofrequency lesioning. It was found that a significantly higher percentage of patients in the treatment group had

Interventional Procedures in Pain Management: An Overview 413

significant reduction in their pain score, global perceived effect and the disability scale at 8 weeks, and the effect was maintained up to 12 months after treatment [52]. Conflicting results were found in another study comparing radiofrequency medial branch neurotomy (n = 36) with a sham procedure (n = 34) for the treatment of lumbar facet joint pain. Apart from an initial improvement at 4 weeks in the functional score in the treatment group, there was no significant difference between the two groups with respect to the pain level and functional disability for up to 12 weeks [22]. With regard to the treatment of cervical facet joint pain after whiplash injury, a study comparing radiofrequency neurotomy for multiple levels of the medial branch (n = 12) to a sham procedure (n = 12) found that by 27 weeks about half of the patients in the treatment group remained free of pain and the treatment group had significantly longer median time for the pain to return to at least 50% of the preoperative level (263 vs 8 days) [26]. In a subsequent systematic view on the use of radiofrequency denervation for neck and back pain, it was concluded that there is limited evidence that radiofrequency denervation had a positive shortterm effect on chronic cervical facet joint pain, but the evidence for chronic lumbar facet joint pain remains conflicting [31].

saline (n = 51) with superficial injection of 1 ml normal saline into the interspinous ligament (n = 48), it was shown that there were highly significant differences in respect of relief of pain and resumption of normal occupation in favour of the group treated by epidural injection for up to 3 months [9]. In another study comparing the same volume of injectate in the treatment group (n = 19) with superficial injection of 2 ml normal saline in the control group (n = 16), it was found that there were significant differences in pain relief compared to the control group for up to 3 months [39]. Positive outcomes were also reported with injection via the caudal route. In one study comparing caudal epidural injection of 80 mg triamcinolone in 25 ml 0.5% procaine (n = 12) with 25 ml of normal saline (n = 11), it was shown that there was significant pain relief and mobility in the treatment group for up to 1 year [6]. Forceful epidural injection has also been shown to be effective for the treatment of lumbosciatic pain in postoperative lumbar spinal fibrosis. In this study, a forceful injection via the caudal route of 125 mg prednisolone acetate and 40 ml normal saline (n = 29) was compared with injection via the same route of corticosteroid alone (n = 31). It was found that significantly higher proportion of patients in the treatment group had relief of sciatica for up to 6 months [38].

Implantable devices

In a systematic review on the efficacy of epidural steroid injections for low back pain and sciatica, of the 12 randomised clinical trials, half reported positive outcomes and the other half reported negative outcomes. It was concluded that the efficacy of epidural steroid injection has not yet been established [21]. It was worth noting, however, that during the time of the earlier studies, fluoroscopy was still not widely practised. In studies that reported negative outcomes, usually only a small volume of injectate was used. In one of the studies, only 2 ml of either 80 mg methylprednisolone or normal saline was injected via the interlaminar approach [48] and in the other the total volume of injectate was only 7 ml [8].

Implantable spinal drug delivery system Spinal opioid has been widely used by anaesthetists in the management of acute postoperative pain. The advantages include higher efficacy of analgesia with lower incidence of adverse effects compared with systemic opioid. Spinal opioid can be given via intrathecal or epidural routes. Intrathecal opioid is usually given as a single injection while epidural opioid can be given through an indwelling catheter inserted percutaneously. The catheter is usually left in situ for only a few days in the postoperative period as there is a potential risk of infection. The use of spinal opioid for chronic pain conditions is made possible by the availability of an implantable spinal drug delivery system. Please refer to Chapter 29 for more details on this technique.

Studies which reported positive outcomes tended to use a larger volume of injectate. In one study comparing the interlaminar epidural injection of 80 mg methylprednisolone in 10 ml normal

There have been few randomised controlled trials and no systematic review of the effectiveness of the implantable spinal drug delivery system in the treatment of refractory cancer pain. In a recent

414 Steven H. S. WONG

randomised clinical trial comparing the use of an implantable intrathecal drug delivery system (n = 71) with comprehensive medical management (n = 72) for refractory cancer pain, it was found that patients using implantable intrathecal drug delivery systems had significant reduction in pain and relief of common drug toxicities, and improvement in survival [47].

Spinal cord stimulation Spinal cord stimulation is based on the gate control theory postulated by Melzack and Wall in 1965 [28], which stated that stimulation of large myelinated A-beta fibres will “close” the gate at the spinal cord to the transmission of nociceptive signals by small unmyelinated C fibres and lightly myelinated A-delta fibres. The first report of electrical stimulation of the spinal cord was published in 1967 by Shealy et al. [45]. Since then, spinal cord stimulation has undergone various developments and generations of technical modifications. It is used in a variety of chronic pain conditions including neuropathic pain associated with failed back surgery syndrome and complex regional pain syndrome, as well as ischaemic pain associated with peripheral vascular disease and angina pectoris. The exact mechanism of action of spinal cord stimulation is still unclear. Studies have shown that the analgesia produced is not mediated by endorphins, as it is not reversible by naloxone. Other mediators have been proposed and they include gamma amino butyric acid, serotonin, substance P, glycine and adenosine [34]. Older generations of spinal cord stimulator used plate electrodes and required implantation via laminectomy by neurosurgeons. Newer generations of electrode leads can be inserted percutaneously and are usually done by the anaesthetists. Trial stimulation is recommended before permanent implantation. Using fluoroscopic guidance, one to two electrode leads are inserted into the epidural space under local anaesthesia. The position of the leads is adjusted so that on stimulation the paraesthesia produced will cover the target region. By varying the combinations of electrodes and the modes of stimulation, the optimal position of the leads can be found. The leads are then implanted subcutaneously and then connected via externalised

wires to an external screener during a trial screening period of about a week, after which implantation of a permanent stimulator will be decided [32]. Please refer to Chapter 30 for more details on spinal cord stimulation. There is a lack of high quality evidence regarding the effectiveness of spinal cord stimulation, the most obvious reason being that it is impossible to achieve blinding. In a systematic review of 39 studies, all case reports, it was found that 50–60% of patients with failed back surgery syndrome achieved greater than 50% pain relief. However, the lack of randomised controlled trials limited the robustness of the conclusions regarding the efficacy of the technique [50]. In a randomised controlled trial comparing spinal cord stimulation plus physical therapy (n = 36) with physical therapy alone (n = 18) for the treatment of complex regional pain syndrome (previously known as reflex sympathetic dystrophy), there was a significant reduction in pain intensity and improvement of health-related quality of life, but not functional status in the group receiving spinal cord stimulation for up to 2 years [18, 19]. However, on long-term follow-up, it was found that the painalleviating effect diminished with time, and was no longer effective after 3 years [20]. In a recent randomised controlled trial, patients who had persistent or recurrent radicular pain after lumbosacral spine surgery were randomised to receive spinal cord stimulation (n = 19) or reoperation (n = 26). It was found that patients initially randomised to receive spinal cord stimulation had significantly lower self-reported pain and higher satisfaction, and were significantly less likely to cross over to alternative treatment. Patients randomised to re-operation required significantly more opioid analgesics [33].

An Algorithmic Approach Despite the lack of strong evidence supporting the long-term efficacy of interventional procedures, their unique diagnostic, prognostic as well as therapeutic roles have enabled them to remain as powerful armamentarium in the management of chronic pain. In order to enhance their efficacy, interventional procedures should be used in an

Interventional Procedures in Pain Management: An Overview 415

algorithmic approach within the context of a multidisciplinary management plan.

local anaesthetics of different durations of action is a reasonable alternative [25].

Before embarking on interventional procedures, the patient should be assessed to identify risk factors that would contribute to the development of chronicity and disability. Psychological factors, notably psychological distress, depressive mood and somatisation, have been shown to be implicated in the maintenance of chronicity [36]. Patients’ illness beliefs and coping such as catastrophising cognitions and fear-avoidance behaviour strongly impede their recovery process [53]. Occupational factors such as low level of job satisfaction, poor workplace conditions, injury at work with ongoing compensation or litigation issues also have important roles in the maintenance of disability and are thus poor prognostic factors for return to work [51]. Social factors such as relationship with spouses or significant others have also been found to influence the pain behaviour [41].

Therapeutic blocks should be considered according to the results of the diagnostic blocks. Prognostic blocks should be performed before contemplation of neuroablative procedures. Before implantation of any permanent devices, an adequate period of trial should be given to the patient to assess the satisfaction and acceptance.

Conclusion

Based on the clinical evaluation, diagnostic blocks should be performed following a strict algorithm. It is important to critically interpret the clinical response to diagnostic blocks as placebo response is often enhanced in patients with chronic pain. Ideally, all diagnostic blocks should include placebo injection with normal saline. However, in clinical practice, the use of comparative blocks using two

The practice of interventional procedures is an essential component in the multidisciplinary management of pain. Despite the lack of evidence regarding their long-term efficacy, their unique diagnostic, prognostic and therapeutic roles are valuable adjuncts to other modes of therapies. It is important to perform them in an algorithmic approach and in accordance with a multidisciplinary treatment plan.

It is also advisable to incorporate interventional procedures into the multidisciplinary treatment programme to facilitate other modes of therapy. For instance, the effect of physiotherapy and exercise therapy would be greatly enhanced by the interruption of nociceptive response after a nerve block. The results of diagnostic blocks can help to alleviate the anxiety of the patients about the causes of the pain.

References Ahadian FM. Pulsed radiofrequency neurotomy: Advances in pain medicine. Curr Pain Headache Rep 2004;8(1):34– 40. 2. Alvarez DJ, Rockwell PG. Trigger points: Diagnosis and management. Am Fam Physician 2002;65(4):653–60. 3. Ambrosini A, Vandenheede M, Rossi P, et al. Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: A double-blind placebo-controlled study. Pain 2005;118(1-2):92–6. 4. Barnsley L, Lord SM, Wallis BJ, et al. Lack of effect of intraarticular corticosteroids for chronic pain in the cervical zygapophyseal joints. N Engl J Med 1994;330(15):1047–50. 5. Breivik H. Chronic pain and the sympathetic nervous system. Acta Anaesthesiol Scand 1997;Suppl 110:131–4. 6. Bush K, Hillier S. A controlled study of caudal epidural injections of triamcinolone plus procaine for the management of intractable sciatica. Spine 1991;16(5):572–5. 7. Carette S, Marcoux S, Truchon R, et al. A controlled trial of corticosteroid injections into facet joints for chronic low back pain. N Engl J Med 1991;325(14):1002–7. 8. Cuckler JM, Bernini PA, Wiesel SW, et al. The use of epidural steroids in the treatment of lumbar radicular pain. A prospective, randomized, double-blind study. J Bone Joint Surg 1985;67(1):63–6. 9. Dilke TF, Burry HC, Grahame R. Extradural corticosteroid injection in management of lumbar nerve root compression. BMJ 1973;2(5867):635–7. 10. Doi K, Nikai T, Sakura S, et al. Intercostal nerve block with 5% tetracaine for chronic pain syndromes. J Clin Anesth 2002;14(1):39–41. 1.

416 Steven H. S. WONG

11. Fishman SM, Smith H, Meleger A, et al. Radiation safety in pain medicine. RegAnesth Pain Med 2002;27(3):296– 305. 12. Garvey TA, Marks MR, Wiesel SW. A prospective, randomized, double-blind evaluation of trigger-point injection therapy for low-back pain. Spine 1989;14(9):962–4. 13. Hameroff SR, Crago BR, Blitt CD, et al. Comparison of bupivacaine, etidocaine, and saline for trigger-point therapy. Anesth Analg 1981;60(10):752–5. 14. Higuchi Y, Nashold B, Sluijter M, et al. Exposure of the dorsal root ganglion in rats to pulsed radiofrequency currents activates dorsal horn lamina I and II neurons. Neurosurgery 2002;50:850–6. 15. Jadad AR, Carroll D, Glynn CJ, et al. Intravenous regional sympathetic blockade for pain relief in reflex sympathetic dystrophy: A systematic review and a randomized, double-blind crossover study. J Pain Symptom Manage 1995;10(1):13– 20. 16. Jankovic J. Botulinum toxin in clinical practice. J Neurol Neurosurg Psychiatry 2004;75:951–7. 17. Kaplan R, Claudio M, Kepes E, et al. Intravenous guanethidine in patients with reflex sympathetic dystrophy. Acta Anaesthesiol Scand 1996;40(10):1216–22. 18. Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med 2000;343(9):618–24. 19. Kemler MA, De Vet HC, Barendse GA, et al. The effect of spinal cord stimulation in patients with chronic reflex sympathetic dystrophy: two years’ follow-up of the randomized controlled trial. Ann Neurol 2004;55(1):13–8. 20. Kemler MA, de Vet HC, Barendse GA, et al. Spinal cord stimulation for chronic reflex sympathetic dystrophy — fiveyear follow-up. N Engl J Med 2006;354(22):2394–6. 21. Koes BW, Scholten RJ, Mens JM, et al. Efficacy of epidural steroid injections for low-back pain and sciatica: A systematic review of randomized clinical trials. Pain 1995;63(3):279–88. 22. Leclaire R, Fortin L, Lambert R, et al. Radiofrequency facet joint denervation in the treatment of low back pain: A placebo-controlled clinical trial to assess efficacy. Spine 2001;26(13):1411–6. 23. Lilius G, Harilainen A, Laasonen EM, et al. Chronic unilateral low-back pain. Predictors of outcome of facet joint injections. Spine 1990;15(8):780–2. 24. Lopez BC, Hamlyn PJ, Zakrzewska JM. Systematic review of ablative neurosurgical techniques for the treatment of trigeminal neuralgia. Neurosurgery 2004;54(4):973–82. 25. Lord SM, Barnsley L, Bogduk N. The utility of comparative local anesthetic blocks versus placebo-controlled blocks for the diagnosis of cervical zygapophysial joint pain. Clin J Pain 1995;11(3):208–13. 26. Lord SM, Barnsley L, Wallis BJ, et al. Percutaneous radiofrequency neurotomy for chronic cervical zygapophyseal-joint pain. N Engl J Med 1996;335(23):1721–6. 27. Marhofer P, Greher M, Kapral S. Ultrasound guidance in regional anaesthesia. Br J Anaesth 2005;94(1):7–17. 28. Melzack R, Wall PD. Pain mechanisms: A new theory. Science 1965;150(699):971–9. 29. Mense S. Neurobiological basis for the use of botulinum toxin in pain therapy. J Neurol 2004;251(Suppl 1):I/1–I7. 30. Nelemans PJ, deBie RA, deVet HC, et al. Injection therapy for subacute and chronic benign low back pain. Spine 2001;26(5):501–15. 31. Niemisto L, Kalso E, Malmivaara A, et al. Cochrane Collaboration Back Review Group. Radiofrequency denervation for neck and back pain: A systematic review within the framework of the Cochrane collaboration back review group. Spine 2003;28(16):1877–88. 32. North RB, Kidd DH, Zahurak M, et al. Spinal cord stimulation for chronic, intractable pain: Experience over two decades. Neurosurgery 1993;32(3):384–94. 33. North RB, Kidd DH, Farrokhi F, et al. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: A randomized, controlled trial. Neurosurgery 2005;56(1):98–106. 34. Oakley JC, Prager JP. Spinal cord stimulation: Mechanisms of action. Spine 2002;27(22):2574–83. 35. Peres MF, Stiles MA, Siow HC, et al. Greater occipital nerve blockade for cluster headache. Cephalalgia 2002;22(7):520– 2. 36. Pincus T, Burton AK, Vogel S, et al. A systematic review of psychological factors as predictors of chronicity/disability in prospective cohorts of low back pain. Spine 2002;27(5):E109–20. 37. Rauck RL, Wallace MS, Leong MS, et al. and Ziconotide 301 Study Group. A randomized, doubled-blind, placebocontrolled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manage 2006;31:393– 406. 38. Revel M, Auleley GR, Alaoui S, et al. Forceful epidural injections for the treatment of lumbosciatic pain with postoperative lumbar spinal fibrosis. Revue du Rhumatisme (English Edition) 1996;63(4):270–7. 39. Ridley MG, Kingsley GH, Gibson T, et al. Outpatient lumbar epidural corticosteroid injection in the management of sciatica. Br J Rheumatol 1988;27(4):295–9. 40. Rocco AG, Kaul AF, Reisman RM, et al. A comparison of regional intravenous guanethidine and reserpine in reflex sympathetic dystrophy. A controlled, randomized, double-blind crossover study. Clin J Pain 1989;5(3):205–9.

Interventional Procedures in Pain Management: An Overview 417

41. Romano JM, Turner JA, Jensen MP, et al. Chronic pain patient-spouse behavioral interactions predict patient disability. Pain 1995;63(3):353–60. 42. Saal JA, Saal JS. Intradiscal electrothermal therapy for the treatment of chronic discogenic low back pain. Clin Sports Med 2002;21(1):167–87. 43. Scrivani SJ, Mathews ES, Maciewicz RJ. Trigeminal neuralgia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100(5):527–38. 44. Shanahan EM, Ahern M, Smith M, et al. Suprascapular nerve block (using bupivacaine and methylprednisolone acetate) in chronic shoulder pain. Ann Rheum Dis 2003;62(5):400–6. 45. Shealy CN, Mortimer JT, Reswick JB. Electrical inhibition of pain by stimulation of the dorsal columns: Preliminary clinical report. Anesth Analg 1967;46(4):489–91. 46. Shealy CN. Facet denervation in the management of back and sciatic pain. Clin Orthop 1976;(115):157–6. 47. Smith TJ, Staats PS, Deer T, et al. Implantable Drug Delivery Systems Study Group. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol 2002;20(19):4040–9. 48. Snoek W, Weber H, Jorgensen B. Double blind evaluation of extradural methyl prednisolone for herniated lumbar discs. Acta Orthop Scand 1977;48(6):635–41. 49. Thomsen HS, Bush WH Jr. Adverse effects of contrast media: Incidence, prevention and management. Drug Saf 1998;19(4):313–24. 50. Turner JA, Loeser JD, Bell KG. Spinal cord stimulation for chronic low back pain: A systematic literature synthesis. Neurosurgery 1995;37(6):1088–95. 51. van der Giezen AM, Bouter LM, Nijhuis FJ. Prediction of return-to-work of low back pain patients sicklisted for 3–4 months. Pain 2000;87(3):285–94. 52. van Kleef M, Barendse GA, Kessels A, et al. Randomized trial of radiofrequency lumbar facet denervation for chronic low back pain. Spine 1999;24(18):1937–42. 53. Vlaeyen JW, Linton SJ. Fear-avoidance and its consequences in chronic musculoskeletal pain: A state of the art. Pain 2000;85(3):317–32. 54. Waldman SD. Atlas of Pain Management Injection Techniques. Philadelphia: WB Saunders Company, 2000. 55. Wepsic JG. Technique for radiofrequency gasserian ganglionectomy. Appl Neurophysiol 1976;39(2):122–32.

418 Steven H. S. WONG

History

Risk factors for chronicity and disability: psychological, occupational, social factors

Organic causes: infection, malignancies

Psychological intervention

Further investigations

Physical examination

Non-localisable pain

Analgesics

Localisable pain

Diagnostic block positive

Diagnostic block negative

Therapeutic block

Physical therapy and rehabilitation

Figure 25.03 An algorithmic approach in the use of interventional procedures in multidisciplinary pain management.

26

Theresa Tak Lai LI

Peripheral Nerve Blocks

Introduction Peripheral nerve blocks are cost-effective anaesthetic techniques used to provide anaesthesia and analgesia. When applied to multidisciplinary pain management, peripheral nerve blocks serve a dual function of both diagnostic and therapeutic tools.

INTRODUCTION ORGANISATION OF THE NERVE BLOCK FACILITY BRACHIAL PLEXUS BLOCK INTERCOSTAL NERVE BLOCK SUPRASCAPULAR NERVE BLOCK OBTURATOR NERVE BLOCK

There are two approaches to the production of differential neural blockade, an anatomical approach and a pharmacological approach. The anatomical approach is based on sufficient anatomical separation of somatic and/or sympathethic fibres. The pharmacological approach is based on the presumed difference in the sensitivity of the various types of nerve fibres to local anaesthetic agents. While differential neural blockade is not intended to replace a detailed history, a complete physical examination, and appropriate laboratory, radiographic and psychological studies, it is pertinent in delineating neural mechanisms in patients with chronic pain. If the pain distribution is limited to one or two peripheral nerves, neurolysis — by placing a needle close to the nerves and either injecting neurodestructive chemicals (phenol or ethanol) or producing neural damage with cold (cryotherapy) or heat (radiofrequency coagulation) — may result in longterm pain relief in selected patients. In this chapter, neural blockades used in pain management will be discussed with an overview of their techniques, indications, relevant anatomy and complications.

MAXILLARY NERVE BLOCK MANDIBULAR NERVE BLOCK SCIATIC NERVE BLOCK REFERENCES

Organisation of the Nerve Block Facility Adequate space, equipment and a comfortable environment are imperative to ensure proper preparation and care of the

420 Theresa Tak Lai LI

patient undergoing regional blockade and advanced interventional pain management procedures. The following issues are essential for smooth running of the regional technique:

Equipment Appropriate and adequate sterile equipment for block procedures are made available prior to commencement of the procedure. Routine maintenance and checking should be performed at regular intervals.

Fluoroscopy Radiological localising is essential for all cases and in particular when difficulty is anticipated due to poor landmarks or anatomical anomalies and when neurolytic procedures are planned.

Monitoring Vital signs recording are mandatory for all procedure especially in cases where monitored anaesthetic care is administered.

Personnel The pain management team comprises the responsible physician, pain nurse and theatre staff familiar with the technique and potential complications of the procedure.

Informed consent The physician should obtain informed consent from the patient in regard to the purpose and technique of the procedure, the expected outcome, the potential side effects and the associated risks.

Guidelines and protocols A set of guidelines and protocols for various procedures should be kept in the procedure theatre for references and should be updated and reviewed in time.

Brachial Plexus Block Brachial plexus block was first performed by two surgeons: Halsted in 1884 and Crile in 1887, with direct exposure in the neck to accomplish the

block [26]. In 1911, Hirschel described the first percutaneous brachial plexus block and since then the efficacy of the procedure has been confirmed and widely used in the field of clinical anaesthesia and pain management [26]. The technique of brachial plexus block is further refined with advanced medical technology by the use of nerve stimulation and sonographic guidance. The four usual sites of approach for brachial plexus blocks are the interscalene space, the supraclavicular area, and the infraclavicular and axillary regions.

Anatomy The brachial plexus is formed by the anterior rami of C5, C6, C7, C8 and T1, with minor contributions from C4 and T2. These nerve roots exit the lateral aspect of the cervical spine to form the plexus and the nerves then pass downward and laterally. Together with the subclavian artery, they run between the anterior and middle scalene muscles passing behind the clavicle and above the top of the first rib to reach into the axilla where they further divide into various terminal branches. The subdivisions can be summarised as below (Fig. 26.01): 1. Roots. They lie in the interscalene groove between the anterior and middle scalene muscles covered by the prevertebral fascia. 2. Trunks. The C5 and C6 roots form the upper trunk, the C7 continues as the middle trunk, and the C8 and T1 roots form the lower trunk. These trunks lie in the same plane as the subclavian artery, with the upper and middle trunks above and the lower trunk posterior to the subclavian artery, in close proximity to the first rib. 3. Divisions. Each trunk divides into anterior and posterior divisions. 4. Cords. The posterior cord is formed by the union of the posterior divisions of all the trunks. The lateral cord is formed by the anterior divisions of the upper and middle trunks. The medial cord is formed by the anterior division of the lower trunk. The posterior, lateral and medial cords are so named due to their relationship with the axillary artery as they lie behind the pectoralis minor muscle. 5. Branches. Peripheral nerves can branch off from the roots, trunks and cords. More commonly encountered in clinical practice are the terminal branches arising from the

Peripheral Nerve Blocks 421

cords. The lateral cord gives off the lateral pectoral nerve, the musculocutaneous nerve and the lateral head of the median nerve. The medial cord gives off the medial pectoral nerve, the medial cutaneous nerve of the arm and forearm, the medial head of the median nerve and the ulnar nerve. The posterior cord gives off the upper and lower subscapular nerves, the nerve to the latissimus dorsi, the axillary nerve to the shoulder joint and the radial nerve. In terms of functional anatomy, motor and sensory innervations of the upper extremity, except for the skin over the upper part of the shoulder (C3, C4) and upper part of the medial arm (T2), are derived from the brachial plexus.

Indications The interscalene and supraclavicular techniques are the preferred methods for brachial plexus block when anaesethesia or relaxation of the shoulder is desired and are commonly used to facilitate surgical operation around the shoulder and above the elbow [26]. The infraclavicular approach is preferred for operations in the forearm and around the elbow. The axillary approach is preferred for operations on the hand and the medial side of the elbow [26]. In acute pain management, brachial plexus block with local anaesthetic agent is used to treat pain due to acute herpes zoster, brachial plexus neuritis, and

Figure 26.01

Drawing of the anatomy of the brachial plexus.

trauma to the shoulder and upper limb [35]. It also serves as a diagnostic tool for evaluation of shoulder and upper extremity pain, and especially in chronic pain conditions such as complex regional pain syndrome [35]. Occasionally, destruction of the brachial plexus may be considered for management of intractable cancer pain due to invasive tumours of the brachial plexus, and tumours of the soft tissue and bone of the shoulder and upper limb. However, a prognostic local anaesthetic block has to be performed prior to neurolysis to assess the degree of motor loss likely to be experienced by the patient.

Procedure The brachial plexus can be targeted in four different approaches: interscalene, supraclavicular, infraclavicular and axillary, adopting different techniques to access the brachial plexus in different regions (Fig. 26.02). Use of a nerve stimulator technique is widely practised in anaesthesia and pain management because it allows fine tuning of needle positioning for optimal placement. The use of nerve stimulation further obviates the need for patient co-operation, thereby allowing use of sedation titrated to individual need and thus enhanced patient satisfaction [5].

Interscalene approach The patient is placed in a supine position with the head turned away from the side to be blocked. The patient is asked to touch the ipsilateral knee to

Figure 26.02 Drawing of the brachial plexus with various approaches shown

422 Theresa Tak Lai LI

depress the shoulder and lift the head to enhance palpation of the lateral border of the clavicular head of the sternomastoid muscle. The cricoid cartilage (C6) is identified and at this level a groove is palpated between the posterior border of the sternomastoid muscle and the anterior scalene muscle. The skin overlying this area is then prepared with antiseptic solution.

also be achieved by electrical stimulation with a current of 0.5 mA at 2 V and endpoints observed are muscle twitches in biceps, triceps and preferably hand muscles for surgery distal to the elbow. After negative aspiration for blood and cerebrospinal fluid, 20 ml of solution is injected and the patient closely monitored for signs of systemic toxicity or inadvertent neuraxial injection.

The block or nerve stimulating needle is inserted at this point perpendicular to the skin in all planes with a slightly caudal and inferior trajectory. The needle is advanced to a depth of around 2 cm such that the needle tip impinges on the brachial plexus as it traverses the interscalene space. When contractions of the muscles at or below the shoulder — either deltoid or biceps twitches — are observed with an initial current of 1.5 mA at 2 V and maintained when the current is reduced to 0.5 mA at 2 V, the needle can be considered to be in the correct place. Once needle position with negative aspiration for blood and cerebrospinal fluid is confirmed, 30 ml of local anaesthetic agent is incrementally injected and the patient closely monitored for signs of systemic toxicity or inadvertent subarachnoid injection.

Infraclavicular approach

Supraclavicular approach The patient is placed in a supine position with a roll between the scapulae. The head is turned away from the side to be blocked. The patient may be asked to lift the head to outline the sternomastoid and scalene muscles. The correct point of needle entry is on the lateral border of the anterior scalene muscle at the midpoint of the clavicle, which is located midway between the acromial end and the sternal end of the clavicle. After sterile preparation of the region, the needle is inserted in a backwardinward-downward manner and perpendicular to all planes at this level in the neck. It should be directed to but not necessarily touching the first rib. Stimulation of the forearm, wrist or digits is elicited at a usual depth of 2 cm. If hand or finger movements are not produced at a depth of more than 2.5 cm, the needle should be withdrawn and re-advanced with a slightly more cephalad trajectory. However, if the first rib is encountered before paraesthesia is elicited, the needle should be walked laterally and slightly posteriorly. Confirmation of the nerves can

There are various ways of conducting the infraclavicular approach to brachial plexus block. The following method uses the nerve stimulation technique. The patient is placed supine with the arm to be blocked abducted to 90° and the head turned away. After the patient’s skin is sterilised, the ground electrode should be attached to the opposite shoulder. The point of needle entry is 2.5 cm below the midpoint of the clavicle. The nerve stimulator needle is introduced through the skin and directed laterally towards the brachial artery and advanced at a 45° angle to the skin. Initial stimulation causes the pectoralis group of muscles to contract and adduct the shoulder and will stop as the needle tip is past the muscles. As the needle approaches the fibres of the brachial plexus, muscles supplied by the musculocutaneous, median, ulnar and radial nerves will contract with each impulse. Clinically, flexion or extension of the elbow (musculocutaneous nerve), palmar flexions of the wrist and flexion of all digits (median nerve), ulnar deviation of the wrist (ulnar nerve) and wrist extension (radial nerve) are observed with stimulation of the respective nerves. When muscle movements are still present at a lowest current level (0.5 mA at 2 V) the needle is in close proximity to the brachial plexus and 30 ml of local anaesthetic agent is incrementally injected.

Axillary approach The axillary block aims to block the terminal branches of the brachial plexus which includes the radial, ulnar and median nerves. The patient is placed in a supine position with the arm abducted 90° at the shoulder joint and elbow. Under sterile conditions, the axillary artery is palpated with one finger and the palpating hand rested on the patient’s arm. The block needle is inserted just proximal to the palpating finger.

Peripheral Nerve Blocks 423

The needle’s position is confirmed by observing movements of the muscles in the hand elicited at a lowest current (less than 1 mA at 2 V) with a nerve stimulator. When needle position is confirmed, the axillary artery is compressed by digital pressure prior to slow injection of anaesthetic solution. This manoeuvre helps to facilitate the proximal spread of injectate to block the musculocutaneous nerve, which leaves the lateral cord high in the axilla.

Complications The proximity of the brachial plexus to the subclavian and axillary arteries and other larger vessels along the course poses potential risk for inadvertent intravascular injection or local anaesthetic toxicity from intravascular absorption. This is particular true for the interscalene approach when a large dose of local anaesthetic agent is required; careful attention should be paid when calculating the total milligram dose of drug that may safely be given. The vascularity also increases the incidence of postblock ecchymosis and haematoma formation. Application of firm pressure and cold packs may reduce the incidence [37]. In addition, the proximity of the brachial plexus to the neuraxial structures and the phrenic nerve can also give rise to complications. Total spinal anaesthesia due to inadvertent intrathecal injection either directly or via extension into a dural cuff has been reported [11]. It should be anticipated that the phrenic nerve will also be blocked with the interscalene and supraclavicular approaches. However, in the absence of significant pulmonary disease, unilateral phrenic nerve block should rarely give rise to disturbance in respiratory function. Owing to the close proximity of the apex of the lung, pneumothorax is a possibility with the supraclavicular technique but less likely with other approaches. Horner’s syndrome is a side effect of brachial plexus block rather than a complication. The sympathetic innervation of the upper extremity is derived from the T1 to T5 spinal segments and the T1 and T2 postganglionic fibres traversing the brachial plexus are often blocked together with the plexus.

New advancements The use of ultrasound for nerve block was first reported by La Grange and colleagues in 1978, when they performed supraclavicular brachial plexus blocks with the help of a Doppler ultrasound

blood-flow detector [14]. The technology and clinical understanding of anatomical sonography have evolved greatly over the past decade. In some centres, ultrasonography has become a routine technique for regional anaesthetic nerve block. Ultrasound guidance enables the operator to secure an accurate needle position in terms of depth and direction, and the ability to monitor the distribution of the local anaesthetic in real time [13]. The risk of local anaesthetic toxicity secondary to intravascular injection is reduced with improved accuracy of needle positioning. This poses additional advantages over conventional guidance techniques such as nerve stimulation to improve the success and quality and thus the onset of anaesthesia/analgesia. Furthermore, the exact location of nerves can be identified to prevent intraneuronal injection and this is particularly useful in patients with difficult anatomical landmarks. The nearby vital structures such as vasculature and pleura are also recognised to avoid unintentional puncture.

Principle of medical ultrasound imaging The ultrasound machine transmits high-frequency sound pulses in the frequency range of 5 to 12 MHz into the body using a hand held probe (Fig. 26.03). The probe of a higher range frequency (10–12 MHz) is selected for superficial approaches while the lower range frequency probe (5–7 MHz) is used on deeper structures. The connective tissue inside the nerves (perineurium and epineurium) and tissue boundaries reflects ultrasound waves. These sound waves are reflected back towards the probe with the greatest amount of reflection achieved when the sound beam is directed nearest to and at 90° to the target. The reflected waves are received by the probe and relayed back to the machine, which calculates the distance from the probe to the organ using the speed of sound in tissue and the time for each reflection. The machine finally displays the distances and intensities of the echoes on the screen, forming a two-dimensional image [6]. Peripheral nerves may appear as hypoechoic (dark) or hyperechoic (bright) sonographic structures, depending on the size of the nerve, the sonographic frequency and the angle of the ultrasound beam [6]. With reference to the brachial plexus, the

424 Theresa Tak Lai LI

Figure 26.05 Interscalene approach with needle advancement along the short axis of the ultrasound probe

Figure 26.03 Photo of an ultrasound machine (with permission of Esaote China Ltd)

Figure 26.06 Transverse sonogram in the interscalene region showing the brachial plexus as hypoechoic nodules (N) between anterior scalene muscle (ASM) and middle scalene muscle (MSM), beneath the posterior margin of the sternocleidomastoid muscle (SCM). CA = carotid artery; IJV = internal jugular vein Figure 26.04 Interscalene approach with needle advancement along the short axis of the ultrasound probe

nerves present as oval echographic structures with hypoechoic predominance in the interscalene and supraclavicular regions or hyperechoic predominance in the infraclavicular region [3, 18]. The vasculature is also recognised as hypoechoic structures and easily distinguished by the presence of pulsations in arteries and the compressibility of veins by the ultrasound probe.

Ultrasound-guided interscalene approach Position the patient supine with the head turned to the opposite side. Perform antiseptic preparation to the skin and the ultrasound probe. Then place a linear high-frequency (10–12 MHz) probe firmly on the neck at the cricoid cartilage level to obtain a cross-sectional view of the brachial plexus (Figs. 26.04 and 26.05). These figures show the operator inserting the needle in the short axis of the ultrasound probe.

Peripheral Nerve Blocks 425

Figure 26.07 Interscalene approach with needle advancement along the long axis of the ultrasound probe in a lateral to medial direction

The following method describes the interscalene approach with needle insertion in the long axis of the ultrasound probe and the brachial plexus blocked in a lateral to medial direction. The trunks appear as an oval hypoechoic structure lying in the interscalene groove between the anterior and middle scalene muscles on ultrasonogram (Fig. 26.06). A 22G x 50 mm insulated short-bevelled block needle is inserted on the lateral end of the ultrasound probe and advanced along the longitudinal or long axis view (Fig. 26.07). This approach allows the needle shaft and tip to be visualised in real time as needle advancement towards the target nerves. The needle creates a dorsal acoustic shadow and is also identified by direct needle movement and tissue displacement. The confirmation of identity of the nerves can be obtained by electrical stimulation as described in the previous section. Once optimal needle position is achieved, the calculated amount of local anaesthetic agent is injected and the spread of solution observed in real time. It is important to fill the needle system with local anaesthetic agent before puncture to avoid air inclusion. A favourable spread should appear as a hypoechoic zone which gradually encircles the nerves and opens up the interscalene groove. If the local anaesthetic spreads in the inappropriate direction, the needle can be repositioned accordingly.

Ultrasound guided supraclavicular approach Position the patient supine with the head turned away from the side to be blocked. Perform antiseptic preparation to the skin and the ultrasound probe. A linear 10–12 MHz ultrasound probe is then placed

Figure 26.08 Transverse sonogram in the supraclavicular region shows brachial plexus as a group of hypoechoic nodules (N) lateral to tha subclavian artery (SA) and cephalad to the first rib (FR). ASM = anterior scalene muscle; MSM = middle scalene muscle; SV = subclavian vein; P = pleura

in the supraclavicular fossa in the coronal plane. A cross-sectional view of the subclavian artery can be seen, and the trunks or divisions of the brachial plexus should appear as oval hypoechoic structures lateral to the subclavian artery and on top of the hyperechoic first rib (Fig. 26.08). Then insert a 22G x 50 mm insulated short-bevelled block needle on the lateral end of the ultrasound probe and advance along the long axis of the probe and in the same plane as the ultrasound beam (Fig. 26.09). The needle creates a dorsal acoustic shadow and is also identified by direct needle movement and tissue displacement. The needle tip and shaft can be visualised in real time as they approach the target nerves. The confirmation of identity of the nerves can be performed by electrical stimulation as described earlier. Fill the needle system with local anaesthetic agent before puncture to avoid air inclusion. Once optimal needle position is achieved, the calculated amount of local anaesthetic is injected and the spread of solution observed in real time. A favourable spread should appear as a hypoechoic zone which gradually encircles the nerves. If the local anaesthetic spread is inadequate and inappropriate, the needle can be repositioned accordingly.

Ultrasound guided infraclavicular approach This approach is based in the anatomical arrangement of the cords of the brachial plexus

426 Theresa Tak Lai LI

The first thoracic ventral branch contributes to the formation of the lower trunk of the brachial plexus. Only a small part continues as the first intercostal nerve. The second intercostal nerve becomes the lateral cutaneous branch and the intercostobrachial nerve, innervating the medial side of the arm. Each of the other intercostal nerves becomes a lateral cutaneous branch innervating the skin of the lateral body wall, and an anterior cutaneous branch innervating the skin of the anterior body wall; skin coverage up to the xiphisternum by the upper six

Figure 26.09 Supraclavicular approach with needle advancement along the long axis of the ultrasound probe in a lateral to medial direction

Figure 26.11 Infraclavicular approach with needle advancement along the long axis of the ultrasound probe in a cephalad to caudad direction

around the second part of the axillary artery. At the infraclavicular level, the lateral cord lies superior and lateral, the posterior cord lies posterior, and the medial cord lies posteroinferior and medial to the axillary artery[18, 19, 30]. The patient lies supine for this procedure. After antiseptic skin preparation, a linear 7 MHz probe is applied medially to the coracoid process underneath the clavicle in a parasagittal plane to obtain a cross-sectional view of the brachial plexus (cords) and the axillary artery.

The pectoral major and minor muscles are seen overlying the pulsatile axillary artery and axillary vein, which are both hypoechoic in appearance (Fig. 26.10). The cords appear hyperechoic, with the lateral cord superior to and the posterior cord posterior to the artery.

Figure 26.10 Transverse sonogram in the infraclavicular region showing the brachial plexus as hyperechoic nodules (L = lateral cord, M = medial cord, P = posterior cord). AA = axillary artery; AV = axillary vein; PMM = pectoralis major muscle; PMiM = pectoralis minor muscle

A 22G x 50 mm insulated short-bevelled block needle is passed in the plane of the ultrasound beam below the clavicle along the long axis of the ultrasound probe and in a cephalad to caudad direction at a 45° angle to the skin (Fig. 26.11). The confirmation of identity of the nerves can be performed by electrical stimulation as described earlier. Fill the needle system with local anaesthetic agent before puncture to avoid air inclusion. Once optimal needle position is achieved, the calculated amount of local anaesthetic agent is injected and the spread of solution observed in real time. This should appear as a hypoechoic zone which gradually encircles the nerves and is most favourably posterior to the axillary artery next to the posterior cord. This manoeuvre invariably will block both the posterior and medial cords. Superficial spread of solution in the pectoralis muscles is often associated with failed block. If feasible, the needle should be withdrawn and redirected towards the anterosuperior position of the axillary artery to achieve a spread of solution to the lateral cord for complete blockade. If the local anaesthetic spread is inadequate and inappropriate, the needle can be repositioned accordingly.

Peripheral Nerve Blocks 427

Ultrasound guided axillary approach The patient is positioned supine with the arm of the side to be blocked abducted at right angles to the body. After antiseptic skin preparation, a 10–12 MHz ultrasound probe is placed in the transverse plane along the axillary crease high up in the axilla. A 22G x 50 mm insulated short-

Figure 26.12 Axillary approach with needle advancement along the long axis of the ultrasound probe in a lateral to medial direction

bevelled block needle is inserted at the lateral end of the ultrasound probe and advanced along the long axis of the probe and in the same plane as the ultrasound beam (Fig. 26.12). A cross-sectional view of the terminal branches of the brachial plexus will appear as round or oval hyperechoic rimmed nodules encircling the hypoechoic axillary artery (Fig. 26.13). The identity of individual branches can be confirmed by electrical stimulation as described in the previous section. Once the needle position is secured, divided doses of the calculated amount of local anaesthetic agent are injected at each nerve location and spread of solution observed in real time. A favourable spread should appear as a hypoechoic zone which gradually encircles the nerves. As mentioned in the description of the anatomy of the brachial plexus, the musculocutaneous nerve originates in the lateral cord high in the axilla. Being located between the coracobrachialis and biceps muscles, it is usually separated from the other nerves at the level of the axilla and is commonly missed by the conventional axillary approach. In most patients, the musculocutaneous nerve can be readily visualised and effectively blocked by injecting another 3 ml of the local anaesthetic after moving the needle and the ultrasound probe slightly in a cranial direction.

Intercostal Nerve Block Indications

Figure 26.13 Transverse sonogram with colour Doppler in the axillary region showing three terminal branches of the brachial plexus as hypoechoic nodules with hyperechoic rims (M = median nerve, U = ulnar nerve, R = radial nerve). AA = axillary artery; AV = axillary vein; MC = musculocutaneous nerve; B = biceps; CB = coracobrachialis; T = triceps

Intercostal nerve block is administered after surgery of the upper abdominal and thoracoabdominal regions for postoperative pain relief. It is also specific and effective for pain relief in fractured ribs [21, 27]. The pain from the chest wall contusion, pleurisy, flail chest and sternotomy or fractured sternum can be successfully controlled with this nerve block [21, 27]. Neurolytic block is performed for pain secondary to bony metastasis to ribs [37].

Anatomy The spinal nerve in the paravertebral region divides into a dorsal branch, innervating the muscle and skin of the back, and a ventral branch which forms intercostal nerves for the 11 intercostal spaces and the subcostal nerve below the last rib.

428 Theresa Tak Lai LI

Figure 26.15

Figure 26.14

Drawing of a needle inside the intercostal space

Drawing of the anatomy of an intercostal nerve

branches and the anterior abdominal wall with T10 around the level of umbilicus by T7 to T11 nerves (Fig. 26.14) [27]. The upper six intercostal nerves innervate the intercostal muscles, and the lower five intercostal nerves and the subcostal nerves innervate the abdominal muscles as well as the intercostals muscles. Each intercostal nerve runs in the neurovascular plane along with an artery and a vein in the costal groove at the inferior border of a rib. This neurovascular plane is between the internal intercostal muscle and the innermost muscle layer consisting of subcostalis, sternocostalis and innermost intercostal muscles (Fig.26.15). Solution injected between the ribs can spread into adjacent spaces and flow medially into the epidural space.

Figure 26.16

Photo of a spinal needle at the angle of the ninth rib

Procedure The intercostal block can be performed at three sites; the angle of the rib posteriorly; the posterior axillary line and midaxillary line laterally; and the anterior axillary line anteriorly. In the classic approach, intercostal nerve block is performed posteriorly at the angle of the ribs and just lateral to the sacrospinalis muscle group (Fig. 26.16). At this point the thickness of the rib is about 8 mm. The patient usually lies in the prone position for the procedure. After the usual skin preparation, the needle entry is made over the rib selected for the block either by manual palpation or more precisely by direct radiological visualisation. The needle should touch the lower half of the rib

Figure 26.17 Radiograph illustrates the spread of contrast along an intercostal nerve

subcutaneously. With one hand holding the needle and syringe, the other hand moves the skin caudally over the rib and thus the needle point “walks” off the lower edge of the rib [34]. The needle is then

Peripheral Nerve Blocks 429

pushed about 3 mm deeper until a slight click is felt as the tip enters the correct space. A small amount of non-ionic contrast medium (Iopamiro 300) is injected to outline the nerve sheath. After negative aspiration for air or blood, either 2 ml 0.5% bupivacaine is injected for diagnostic or prognostic block, or 2 ml 10% phenol in Conray contrast medium is injected for neurolytic block with a direct view of injectate spread on fluoroscopy (Fig. 26.17).

due to trauma to the shoulder joint and girdle [10, 16, 29, 40]. Suprascapular nerve block has also been employed for shoulder and upper extremity chronic pain conditions, such as rheumatoid arthritis, frozen shoulder with pain syndrome in reflex sympathetic dystrophy or adhesive capsulitis to facilitate a physical rehabilitation programme [36]. Destruction of the suprascapular nerve is indicated for palliation of cancer pain involving the shoulder girdle of either primary or secondary origin.

Complications

Anatomy

Inadvertent needle puncture of the pleura can cause a pneumothorax. Careful performance reduces the risk of this complication. If, however, it occurs, it can be easily managed by observation, with or without simple aspiration; very occasionally is chest drain required.

The suprascapular nerve is formed from the C5 and C6 nerve roots of the brachial plexus. The nerve leaves the brachial plexus inferiorly and posteriorly and passes underneath the coracoclavicular ligament and through the suprascapular notch of the scapula with the corresponding suprascapular artery and vein. The suprascapular nerve innervates the shoulder joint and to a certain extent the motor supply of the supraspinatus and infraspinatus muscles (Figure 26.18) [28].

Accidental intravascular injection causes systemic toxicity. The intercostal space is supplied by a rich network of vasculature and because of the high metabolic activity of the intercostal muscle, there is high absorption of local anaesthetic agents leading to high plasma level and peak sooner than when the same amount of local anaesthetic agent is injected elsewhere. Thus, attention should be paid to the total dosage of drug used and negative aspiration confirmed prior to every injection. The third complication is the development of a subarachnoid block. This complication has been reported and proven by dye studies [21]. The dura occasionally extends out along intercostal nerves for a variable distance before it adheres to the nerve as the neurilemma. In this situation, drug deposited in this potential space can spread into the subarachnoid and result in spinal anaesthesia, which clinically presents with sudden and significant hypotension. This is particularly likely when the point of needle entry is directed too medially [37].

Procedure The patient is placed in the prone position with the arms at the side to be blocked. The spine of the scapula is identified and palpated laterally to the acromion. With the skin prepared with antiseptic solution, the point of needle entry is where the thicker acromion fuses with the thinner scapular spine. The needle should hit the scapular bone at a depth of about 2 cm and then gently “walked” superiorly and medially until the tip walks off

Suprascapular Nerve Block Indications Suprascapular nerve block with local anaesthetic is used as a clinical diagnostic tool to evaluate shoulder joint pain [33]. It provides acute pain relief in postoperative pain for shoulder surgery and pain

Figure 26.18 Drawing of the posterior of a scapula showing the anatomy of a suprascapular nerve

430 Theresa Tak Lai LI

Figure 26.19 Photo of a needle at the suprascapular notch

Figure 26.21 Radiograph of a needle at the suprascapular notch

Figure 26.20 Radiograph of a pointer at the suprascapular notch Figure 26.22

the scapula body into the suprascapular notch (Fig. 26.19). A paraesthesia is often elicited as the needle makes contact with the nerve [36]. The needle should not be advanced more than 1 cm further to prevent the risk of pneumothorax. An anteroposterior fluoroscopic image provides direct visualisation of the needle as it makes contact with the scapular bone and traverses the suprascapular notch. Further confirmation of the position of the needle can be seen when the contrast solution fills the suprascapular notch and runs towards the glenoid cavity (Figs. 26.20 to 26.22). With the needle in the optimal position, 5–10 ml of 0.5% bupivacaine for diagnostic block or 3–5 ml 10% phenol in Conray contrast medium is injected for neurolytic block. When treating painful conditions that are mediated via the suprascapular nerve,

Radiograph of contrast spread along the suprascapular nerve

40 mg depomedrol is often added to the local anaesthetic.

Complications The close proximity of the suprascapular vasculature increases the risk of inadvertent intravascular injection and possible local anaesthetic systemic toxicity. Thus meticulous care should be taken in calculating the total safe dose of agent to be given. Pneumothorax is also a potential technical complication if the needle is advanced too deep through the suprascapular notch causing pleural puncture.

Peripheral Nerve Blocks 431

Obturator Nerve Block Indications An important indication of obturator nerve block is based on its anatomical relationship as it runs along the neck of the bladder and the prostate. Due to the proximity of this nerve to the prostate, is can be electrically stimulated during transurethral resection surgery. This leads to significant contraction of the adductors which can interfere with the surgical procedure, and serious complications such as bladder wall perforation with secondary infection and tumour dissemination have been reported [1]. This can occur despite adequate spinal anaesthesia with complete blockade of nerve roots proximal to the site of stimulation. Obturator nerve block with local anaesthetic has been shown to effectively abolish the adductor spasms during transurethral prostatic surgery [17]. The addition of an obturator nerve block to femoral and sciatic blockade is also performed to improve postoperative analgesia following total knee replacement [12, 15]. Adductor muscle spasticity is problematic in patients with neurological sequelae of stroke, head trauma, spinal cord injury, cerebral palsy or any lesion of the motor neurone. In rehabilitation medicine, obturator nerve block has been extensively used in the management of patients with adductor muscle spasticity to reduce spasm and associated pain, and improve gait and hygienic care [31, 32, 39]. Obturator nerve block can be used as a diagnostic tool for complex pain problems involving the hip and nearby area. Cases of obturator nerve entrapment have been reported in athletes and in patients after pelvic surgery and a diagnostic obturator nerve block can provide information to make a clinical diagnosis.

Anatomy The obturator nerve is formed from the anterior primary rami of L2 to L4 with contribution of L3 predominant. The nerve passes through the psoas muscle and leaves the muscle at the lateral border. It then travels posterior to the iliac vessels and reaches the undersurface of the superior pubic ramus and emerges through the obturator foramen along with the obturator artery (Fig. 26.23). At this point the obturator nerve divides into the anterior and the posterior branches. The obturator nerve

Figure 26.23

Drawing of the anatomy of an obturator nerve

is predominantly a motor nerve with the anterior branch innervating the anterior adductor muscles and the posterior branch innervating the adductor magnus muscles. Is has a variable cutaneous sensory supply to the hip and knee joints, and an area along the medial aspect of the thigh.

Procedure The patient is placed in a supine position and the legs slightly abducted. The procedure is performed under sterile conditions after antiseptic skin preparation. A 22G x 50 mm insulated block needle is inserted almost perpendicularly to the skin, 1–2 cm caudally and 1–2 cm laterally to the pubic tubercle. The needle is advanced until it contacts the inferior border of the superior pubic ramus bone and is then tilted almost 90° and redirected posteriorly and slightly laterally to walk off the inferior margin of the superior pubic ramus. The needle trajectory can be more precisely seen with fluoroscopic guidance, which also allows direct visualisation of the pubic ramus and the obturator foramen. First obtain an anteroposterior image of the pelvis and then the fluoroscope is rotated in a cephalocaudad projection to view the pubic ramus and obturator foramen directly in line with the fluoroscopy beam. The point of skin entry remains the same but the needle is aimed along the axis of the fluoroscopy beam towards the lateral end of the superior pubic ramus and then passed underneath the inferior edge to enter the obturator foramen (Fig. 24.25). The needle should not be advanced more than 3 cm from this point to prevent pelvic organ damage.

432 Theresa Tak Lai LI

The location of the obturator nerve is detected with the aid of the nerve stimulator during needle advancement by eliciting strong adductor muscle contraction with a current of 0.5 mA at 2 V. A small amount of non-ionic contrast medium is injected to outline the nerve on fluoroscopy (Fig. 26.26). After optimal needle position is confirmed

and negative aspiration, 10 ml of local anaesthetic (0.5% bupivacaine) or 5–10 ml of neurolytic agent (10% phenol in contrast medium) is injected incrementally.

Complications Careful location of anatomical landmarks and the use of fluoroscopy significantly reduce the incidence of serious complications. The most commonly seen complication is haematoma or ecchymosis in the inguinal region post block. This is likely if the obturator artery which travels with the obturator nerve is inadvertently punctured. If the needle is advanced too deep into the pelvis (more than 3 cm), the risk of damage to pelvic organs such as the bladder is possible.

Maxillary Nerve Block Indications

Figure 26.24 Radiograph of needle at the inferior border of the superior pubic ramus

The maxillary nerve block can be performed for analgesia during maxillofacial surgery involving the upper jaw [25]. It may also be used as a diagnostic tool in chronic facial pain syndrome. Therapeutic maxillary nerve block with a neurolytic agent is used to treat painful tumours of the anterior

Figure 26.25 Radiograph of needle at the inferior border of the superior pubic ramus

Figure 26.26 Radiograph of bilateral obturator nerves outlined with contrast agent

Peripheral Nerve Blocks 433

antrum [23]. Maxillary nerve block with local anaesthetic or steroids is an excellent adjunct to the pharmacological treatment in trigeminal neuralgia and acute herpes zoster infection in the distribution of second division of the trigeminal nerve.

Anatomy The maxillary nerve constitutes the second division of the trigeminal nerve. It is a pure sensory nerve which travels anteroinferiorly and exits through the foramen rotundum and enters the sphenopalatine fossa (Fig. 26.27). The maxillary nerve gives off branches to supply the upper jaw, teeth, gums, hard and soft palate, and cheek. It also contains some parasympathetic fibres. The maxillary nerve then passes through the infraorbital foramen and becomes the infraorbital nerve, which supplies the sensation from the lower eyelid to the upper lip.

Procedure The patient is placed supine with the head straight and appropriate skin antiseptic preparation applied. The coronoid notch is identified by asking the patient to open and close the mouth or by direct visualisation under a lateral fluoroscopic beam. A 22G x 7.5 cm spinal needle is directed perpendicular to the skin through the coronoid notch below the midpoint of the zygomatic arch. The needle is advanced until it contacts the lateral pterygoid plate. The needle is then withdrawn and redirected anteriorly and superiorly at a 45° angle towards the

Figure 26.28 Needle placement at the maxillary nerve via the coronoid notch

roof of the nose (Fig. 26.28). The needle should not be advanced more than 1 cm past the pterygoid plate. Once the needle is positioned and negative aspiration for blood and cerebrospinal fluid (CSF) confirmed, local anaesthetic (0.5% bupivacaine) is injected slowly: 1–3 ml for diagnostic block, or 3–5 ml followed by 1 ml of neurolytic agent (10% phenol) for therapeutic block.

Complications Facial ecchymosis and haematoma associated with the procedure are usually self-limiting. Precautions should be taken to prevent the needle advancing too deeply and in a cephalad direction to avoid entering the infraorbital fissure and possibly damaging the optic nerve. Drug deposited in this region can also spread to the posterior aspect of the orbit and the optic nerve producing blindness. Inadvertent intravascular and subarachnoid injections are potential lethal side effects.

Mandibular Nerve Block Indications

Figure 26.27 Drawing of the Gasserian ganglion in the middle cranial fossa and the course of the three divisions and distal branches

The mandibular nerve block provides effective pain relief for surgical reduction of fractured mandible. It may be used as a diagnostic tool in chronic facial pain syndrome. It is useful for palliation of pain secondary to malignancy of the tongue, lower jaw and floor of the mouth [24]. Mandibular nerve block with local anaesthetic or steroids is an

434 Theresa Tak Lai LI

excellent adjunct to the pharmacological treatment in trigeminal neuralgia and acute herpes zoster infection in the distribution of third division of the trigeminal nerve V3.

Anatomy The mandibular nerve is the third division of the trigeminal nerve. It consists of a large sensory root and a small motor root. It travels inferolaterally and exits through the foramen ovale where it immediately divides into two branches, the anterior and posterior branches (Fig. 26.27). The anterior branch supplies motor fibres to the muscles of mastication and only supplies sensation to the lateral face and underlying mucosa by the buccal nerve. The larger posterior branch is mostly sensory and further divides into the auriculotemporal nerve, the inferior dental nerve and the lingual nerve. The auriculotemporal nerve emerges from behind the temporomandibular joint to supply sensation to the external auditory meatus and temple. The inferior dental nerve enters the ramus of the mandible to run through the bone and emerge at the mental foramen as the mental nerve. The lingual nerve runs in an inferolateral direction to reach the medial side of the ramus of the mandible and supply the anterior two thirds of the tongue and inferior jaw.

Figure 26.29 Needle placement at the mandibular nerve via the coronoid notch

Complications Facial ecchymosis and haematoma associated with the procedure are usually self-limiting. Inadvertent intravascular and subarachnoid injections are potential lethal complications. The needle can enter the pharynx if it is advanced too deep with the possibility of puncturing the middle meningeal artery, which enters the cranium through the spinous foramen.

Procedure The patient is placed in a supine position with appropriate skin antiseptic preparation. The coronoid notch is identified by asking the patient to open and close the mouth or by direct visualisation under lateral fluoroscopic beam. A 22G x 7.5 cm spinal needle is directed perpendicular to the skin through the coronoid notch below the midpoint of the zygomatic arch. The needle is advanced until it contacts the lateral pterygoid plate. At this point, the needle is walked backwards off the pterygoid plate with the same depth maintained (Fig. 26.29). A paraesthesia of the lower lip, lower jaw or tongue is elicited preferably. Once the needle is positioned and negative aspiration for blood and cerebrospinal fluid (CSF) confirmed, local anaesthetic (0.5% bupivacaine) is injected slowly: 1–3 ml for diagnostic block, or 3–5 ml followed by 1 ml of neurolytic agent (10% phenol) for therapeutic block.

Sciatic Nerve Block Labat first described the posterior approach to the sciatic nerve in 1923 [23]. Various other methods of sciatic nerve block have since then been introduced, for example ,the anterior approach proposed by Raj and associates in 1975 [23]. In recent times, ultrasound-guided location of the nerve with electrical stimulation confirmation has been widely used in clinical anaesthesia.

Anatomy The sciatic nerve is formed from the nerve roots of L4 to L5 and S1 to S3 in the lumbosacral plexus. It leaves the pelvis and enters the gluteal region through the greater sciatic foramen and passes through a tunnel between the greater trochanter and the ischial tuberosity (Fig. 26.30). In the buttocks, it runs underneath the piriformis muscle,

Peripheral Nerve Blocks 435

Figure 26.30

Drawing of the anatomy of the sciatic nerve

posterior to the gemelli and obturator muscles, and anterior to the gluteus maximus muscle. The sciatic nerve courses down the posterior thigh and divides into the tibial and common peroneal nerves in the popliteal fossa.

Figure 26.31 Patient position for posterior approach to sciatic nerve block. IT= Ischial tuberosity; GT = greater tuberosity

Ultrasound scanning guided technique A subgluteal approach is used with the patient placed in a semi-prone position with the block limb

Indications The sciatic nerve is commonly blocked for surgery and analgesia involving the foot and ankle.

Technique Posterior approach Classically the posterior approach is performed with the patient placed in the semi-prone position with the side to be blocked uppermost and the hip and knee flexed. The gluteal region is then sterilised and draped. The prominence of the greater trochanter and posterior superior iliac spine is located and a line joining these two points drawn (Fig. 26.31). At the midpoint, a 4 cm perpendicular line is then drawn caudally. A skin wheal is raised and a 22G needle is inserted perpendicular to the skin and the sciatic nerve is usually contacted at 4 to 6 cm from skin. A peripheral nerve stimulator can be used to achieve more accurate location of the sciatic nerve. A 21G x 10 cm insulated block needle is inserted in a similar manner and the electrical stimulation set a current of 0.5m A at 1–2 Hz. Dorsiflexion or plantar flexion of the foot should be observed for needle confirmation. A 20-ml volume of local anaesthetic agent can be injected in divided doses after negative aspiration for blood.

Figure 26.32 An ultrasound probe placed along a line joining the ischial tuberosity and the greater trochanter

436 Theresa Tak Lai LI

uppermost. The bony prominence of the greater trochanter laterally and the ischial tuberosity medially are marked and a line drawn between these two points. The midpoint along this line marks the approximate sciatic nerve location. After skin preparation, a 10–15 MHz ultrasound probe in placed over the subgluteal region in a transverse plane (Fig. 26.32). The sciatic nerve is seen as hyperechoic on ultrasonography along a plane between the ischial tuberosity medially and the greater trochanter laterally (Fig. 26.33). A 21G x 10 cm insulated block needle is inserted perpendicular to the ultrasound probe (Fig. 26.34). When the needle in is close proximity and contacts the nerve, tissue or nerve movement can be seen. The position of the needle is confirmed by electrical stimulation to the sciatic nerve as described previously. When the needle position is satisfied by nerve stimulation and motor response, 20 ml of local anaesthetic is injected under ultrasound visualization. This should appear as circumferential spread of hypoechoic local anaesthetic agent around the hyperechoic nerve bundles. The sciatic nerve can be scanned proximally and distally to observe longitudinal spread of drug.

Figure 26.33 The sciatic nerve appears as a hyperechoic oval shape in a plane between the ischial tuberosity medially and greated trochanter laterally

Complications Potential complications include bleeding, intravascular injection, intraneural injection and possible residual dysaesthesiae.

Figure 26.34

Needle insertion under the guidance of ultrasonography

References 1. 2. 3. 4. 5. 6. 7. 8. 9.

Akata T. Life-threatening haemorrhage following obturator artery injury during transurethral bladder surgery: A sequel of an unsuccessful obturator nerve block. Acta Anaesthesiol Scand 1999;43(7):784–8. Bradshaw C, McCrory P. Obturator nerve entrapment. Clin J Sport Med 1997;7(3):217–9. Chan VWS, Perlas A, Rawson R, et al. Ultrasound-guided supraclavicular brachial plexus block. Anesth Analg 2003;97:1514–7. Chan VWS. Applying ultrasound imaging to interscalene brachial plexus block. Reg Anesth Pain Med 2003;28(4):340– 3. Choyce A, Chan WV, Middleton WJ, et al. What is the relationship between paraesthesia and nerve stimulation for axillary brachial plexus block? Reg Anesth Pain Med 2001;26(2):100–4. Dabu A, Chan VWS. A Practical Guide to Ultrasound Imaging for Peripheral Nerve Blocks. Toronto: University of Toronto, 2004. Deliveliotis C, et al. The contribution of the obturator nerve block in the transurethral resection of bladder tumors. Acta Urol Belg 1995;63(3):51–4. Gasparich JP, et al. Use of nerve stimulator for simple and accurate obturator nerve block before transurethral resection. J Urol 1984;132(2):291–3. Greher M, Kapral S. Is regional anesthesia simply an exercise in applied sonoanatomy?: Aiming at higher frequencies of ultrasonographic imaging. Anesthesiology 2003;99(2):250–1.

Peripheral Nerve Blocks 437

10. 11. 12. 13. 14. 15.

16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40.

Jones DS, Chattopadhyay C. Suprascapular nerve block for the treatment of frozen shoulder in primary care: A randomized trial. Br J Gen Pract 1999;49(438):39–41. Korman B, Riley R. Convulsion induced by ropivacaine during interscalene brachial plexus block. Anesth Analg 1997;85:1128–9. Macalou D, Trueck S, Meuret P, et al. Postoperative analgesia after total knee replacement: The effect of an obturator nerve block added to the femoral 3-in-1 nerve block. Anesth Analg 2004;99:251–4. Marhofer P, Greher M, Kapral S. Ultrasound guidance in regional anaesthesia. Br J Anaesth 2005;94(1):7–17. Marhofer P, Willschke H, Greher M, et al. New perspectives in regional anesthesia: The use of ultrasound — past, present, and future. Can J Anaesth 2005;52(6):R1–R. McNamee DA, Parks L, Milligan KR. Postoperative analgesia following total knee replacement: An evaluation of the addition of an obturator nerve block to combined femoral and sciatic nerve block. Acta Anaesthesiol Scand 2002;46(1):95–9. Neal JM, McDonald SB, Larkin KL, et al. Suprascapular nerve block prolongs analgesia after non-arthroscopic shoulder surgery but does not improve outcome. Anesth Analg 2003;96:982–6. Ong EL, et al. Transurethral surgery and the adductor spasm. Ann Acad Med Singapore 2000;29(2):259–62. Perlas A, Chan VWS, Simons M. Brachial plexus examination and localization using ultrasound and electrical stimulation: A volunteer study. Anesthesiology 2003;99(2):429–35. Porter JM, McCarney CJL, Chan VWS. Needle placement and injection posterior to the axillary artery may predict successful infraclavicular brachial plexus block: A report of three cases. Can J Anaesth 2005;52(1):69–73. Raj PP, Lou L, Erdine S, et al. Radiographic Imaging for Regional Anesthesia and Pain Management. New York: Churchill Livingstone, 2003;111–6. Raj PP, Lou L, Erdine S, et al. Radiographic Imaging for Regional Anesthesia and Pain Management. New York: Churchill Livingstone, 2003;117–22. Raj PP, Lou L, Erdine S, et al. Radiographic Imaging for Regional Anesthesia and Pain Management. New York: Churchill Livingstone, 2003;245. Raj PP, Lou L, Erdine S, et al. Radiographic Imaging for Regional Anesthesia and Pain Management. New York: Churchill Livingstone, 2003;49. Raj PP, Lou L, Erdine S, et al. Radiographic Imaging for Regional Anesthesia and Pain Management. New York: Churchill Livingstone, 2003;53. Raj PP. Textbook of Regional Anesthesia. New York: Churchill Livingstone, 2002;338–9. Raj PP. Textbook of Regional Anesthesia. New York: Churchill Livingstone, 2002;341–50. Raj PP. Textbook of Regional Anesthesia. New York: Churchill Livingstone, 2002;356–8. Raj PP. Textbook of Regional Anesthesia. New York: Churchill Livingstone, 2002;575–6. Ritchie ED, Tong D, Chung F, et al. Suprascapular nerve block for postoperative pain relief in arthroscopic shoulder surgery: A new modality? Anesth Analg 1997;84:1306–12. Sandhu NS, Capan LM. Ultrasound-guided infraclavicular brachial plexus block. Br J Anaesth 2002, 89(2):254–9. Trainer N, et al. Obturator nerve block for painful hip in adult cerebral palsy. Arch Phys Med Rehabil 1986;67(11):829– 30. Viel EJ, et al: Neurolytic blockade of the obturator nerve for intractable spasticity of adductor thigh muscles. Eur J Pain 2002;6(2):97–104. Waldman SD. Atlas of Interventional Pain Management, 2nd edn. Philadelphia: WB Saunders, 2004;145–7. Waldman SD. Atlas of Interventional Pain Management, 2nd edn. Philadelphia: WB Saunders, 2004; 228–31. Waldman SD. Interventional Pain Management, 2nd edn. Philadelphia: WB Saunders, 2001;382. Waldman SD. Interventional Pain Management, 2nd edn. Philadelphia: WB Saunders, 2001;388–9. Waldman SD. Interventional Pain Management, 2nd edn. Philadelphia: WB Saunders, 2001;396. Waldman SD. Interventional Pain Management, 2nd edn. Philadelphia: WB Saunders, 2001;401. Wassef MR. Interadductor approach to obturator nerve blockade for spastic conditions of adductor thigh muscles. Reg Anesth 1993;18(1):13–7. Wassef MR. Suprascapular nerve block. A new approach for the management of frozen shoulder. Anaesthesia 1992;47(2):12–4.

27

Philip FINCH

The Sympathetic Chain: Efficacy of Sympathetic Blockade and Sympathectomy Introduction

INTRODUCTION HISTORY ANATOMICAL BASIS OF SYMPATHETIC BLOCKS SYMPATHOLYSIS AND SYMPATHETIC BLOCKADE IN PERIPHERAL VASCULAR DISEASE SYMPATHOLYSIS IN THE TREATMENT OF ABDOMINAL VISCERAL PAIN Anatomy of coeliac plexus Anatomy of splanchnic nerves Coeliac plexus blockade Splanchnic nerve neurolysis HYPOGASTRIC PLEXUS AND GANGLION OF IMPAR NEUROLYSIS Neurolysis of the superior hypogastric plexus Ganglion of impar neurolysis

From its first description by Gaskell and Langley in 1889, few structures in the body have received as much enthusiastic but inappropriate attention as the sympathetic chain. Only in recent times, with improved trial data, has a clearer view appeared. This is especially so in the field of pain medicine, where sympathetic blockade is often placed among the first lines of treatment [51] despite little evidence to support this practice. The theory of “sympathetic efferent hyperactivity” has never been substantiated and blockade of the chain is perhaps based on a false premise [15, 107]. In many instances, the placebo arm of randomised controlled trials of sympathetic blockade in the treatment of pain states has been as equally effective as the active treatment. Some even consider blockade of the sympathetic chain to be a futile procedure [96]. But should we consider sympathetic blockade to be totally without merit? The answer probably lies somewhere between the opposing views. Few could argue that the pain of upper gastrointestinal cancer would not be greatly improved with splanchnic and coeliac plexus blockade [24, 69]. Vascular ulcers in the elderly can often be induced to heal with lumbar sympathectomy [21]. Socially devastating hyperhidrosis, especially in young women, can be significantly reduced but perhaps with unacceptable sequelae [121]. Even sympathetic blockade for complex regional pain syndrome (CRPS) may have a place with careful patient selection [28]. This chapter will examine the role of sympathetic blockade in the treatment of a number of conditions. It will span the more traditional use of sympathectomy for peripheral vascular disease and visceral pain in gastrointestinal cancer to the more contentious indications such as the treatment of hyperhidrosis and neuropathic pain states. It will also examine the evidence in support of such practices. But, first let us examine the

440 Philip FINCH

history of sympathetic blockade and sympathectomy, for it can provide valuable lessons in the use and abuse of an interventional technique. The chapter will not act as a primer for performing these blocks, except in outline, as more detailed descriptions exist elsewhere [84, 106].

History In 1889, the same year that the anatomy of the sympathetic chain was described, the first surgical sympathectomy was performed in the treatment of epilepsy! Surgical removal of the stellate ganglion was then tried for varied conditions such as exophthalmos, glaucoma, trigeminal neuralgia and even optic atrophy. A more logical approach then prevailed following the description by Leriche of periarterial stripping for Raynaud’s disease and later for causalgia [60, 61]. It is of interest that there is a modern equivalent of this technique in the treatment of refractory hand pain and ulceration [54]. Likewise, causalgia (CRPS II), first described by Mitchell in the American Civil War 1861–1865 [68] was treated by sympathectomy in World Wars I and II [33, 62] and in recent conflicts such as the Iran-Iraq War 1980–1988 [39]. Figure 27.01 Rene Leriche (1879 – 1955)

COSMETIC INDICATIONS FOR SYMPATHETIC NEUROLYSIS Anatomy of the cervicothoracic chain Endoscopic thoracic sympathectomy SYMPATHETIC BLOCKADE AND SYMPATHECTOMY IN THE TREATMENT OF PAIN STATES CONCLUSION REFERENCES

Intravenous regional local anaesthetic blockade also has a long history and was first described by Bier in 1908. Various drugs which are active at the peripheral adrenergic receptor have been added to local anaesthetic agents, and have been used in regional techniques over the years, mainly in the treatment of pain states such as CRPS. The results have not been encouraging [48], despite early enthusiasm [37]. Again, the placebo has been shown to be equally effective as drugs such as guanethidine, which is now seldom used in the treatment of CRPS. Direct blockade of the sympathetic chain with local anaesthetic agents in the treatment of CRPS has also proved no more efficacious when subjected to randomised placebo controlled trials (RCT). In a recent systematic review of RCTs and non-randomised trials in the treatment of CRPS, only one-third of patients reviewed responded fully to sympathetic blockade, which is little different to a placebo response [17]. These inconclusive results were mirrored in a later study by the same authors regarding short-term effects of sympathetic blockade in the treatment of CRPS [16]. This author had previously found that only approximately 50% of patients with CRPS respond to sympathetic blockade with more than temporary thermoregulatory changes [28]. Longer-term sympatholysis such as surgical sympathectomy produce such poor results that these techniques have largely been abandoned in the treatment of

The Sympathetic Chain 441

pain states such as CRPS. Unfortunately, instead of the intended effects, complicating sequelae such as compensatory sweating can be the only longterm results of surgical ablation of the sympathetic chain. Kotzareff in 1920, successfully treated upper limb hyperhidrosis by excision of the cervical ganglia but unfortunately caused a Horner’s syndrome in the process [55]. The thoracoscope is now frequently used to access the upper thoracic ganglia for the same indication, but unfortunately still with unacceptable outcomes in some instances [57]. In a recent extensive case series, there was a 3.8% incidence of Horner’s syndrome in patients undergoing thoracoscopic sympathectomy [121]. This can be a devastating complication in a young person. There are even suggestions that sympathectomy may be helpful in the management of social phobic reactions [100]. In fact, endoscopic sympathectomy is recommended as the preferred treatment in severe, “conservative therapy resistant” social phobia [52]. It would appear that not a lot has changed in over 100 years. In 1924, Royle in Australia resected the lumbar sympathetic chain both in animal models and humans, hoping to modify skeletal muscle tone in patients with spastic paralysis [91]. He noted vasomotor effects and subsequently applied this finding to the treatment of Raynaud’s disease [92]. Thoracoscopic sympathectomy for Raynaud’s phenomenon has also been subjected to longterm follow-up [101]. Unfortunately, symptoms recurred in a substantial percentage of patients in the follow-up period and many regretted having the operation. In more recent times, techniques for sympathetic blockade have been modified with advances in imaging. In the cervicothoracic, splanchnic and lumbar regions, direct vision endoscopic procedures have supplemented the use of the Carm image intensifier and computed tomography (CT) guidance [27]. Also, novel techniques for approaching the sympathetic ganglia have perhaps improved the safety of sympatholytic interventions [13]. However, the rationale for using sympatholysis in the first place for the treatment of various conditions is less than convincing and increasingly subjected to critical evaluation. It is possible that

sympatholysis will eventually disappear from treatment schedules proposed by pain physicians and vascular and cosmetic surgeons alike, as its true efficacy becomes better understood and the rate of complications is rejected by both patients and physicians.

Anatomical Basis of Sympathetic Blocks Much of the detailed anatomy of the sympathetic chain will be examined in the sections relating to specific techniques for the four main areas of interest. These include the cervicothoracic ganglia, the splanchnic-coeliac plexus, the lumbar ganglia and the superior hypogastric plexus. The sympathetic nervous system has both central and peripheral parts. The central component includes the hypothalamus, midbrain, pons, medulla and lateral columns of the spinal cord from T1 to L2. The central component connects in the thoraco-lumbar region to two ganglionated nerve trunks extending from the first cervical level to the coccyx. Preganglionic fibres, which are myelinated fibres, ramify both cranially and caudally, so that ongoing synaptic connections to the spinal nerves can occur at both several segments above and below the entry of the white rami into the chain. Not all nerve fibres are efferent and mention must be made of sympathetic afferents, which are largely unmyelinated and traverse the coeliac ganglion without synapse, some fibres crossing the midline, and then travelling centrally via the splanchnic nerves to the sympathetic ganglia and thence to the sympathetic axonal cell bodies in the dorsal roots T5–T10 [115]. It is these afferent fibres that are blocked in neurolytic procedures for abdominal cancer pain. Sympathetic ganglia, which are said to number five in the lumbar region, five in the sacral region and three in the cervical region [88], however, show considerable variability in position and number and may even interconnect across the midline [22, 79, 104, 112]. It is the variability in the anatomy of the sympathetic ganglia that can produce unpredictable results in techniques such as radiofrequency sympatholysis of the lumbar chain.

442 Philip FINCH

Sympatholysis and Sympathetic Blockade in Peripheral Vascular Disease Possibly one of the less contentious uses of sympathetic blockade, lumbar sympatholysis by paravertebral block, became established in the 1920s after the work of Brunn and Mandl in Vienna [23] and Royle in Australia [91]. Chemical sympathectomy, which is popular to this day for assisting in the healing of vascular ulcers and relieving rest pain, is a safe procedure for the aged and infirm. This simple technique can avoid the need for general anaesthesia and is performed as an outpatient procedure. Aqueous phenol 10%, which was popularised by Haxton in 1949, has largely replaced alcohol as it reduces the incidence of neuritis. Its use for the upper thoracic chain has been described [27], but has never achieved the same popularity as lumbar chemical sympathectomy, possibly due to the technical difficulty of nerve blocks in the vicinity of the lung, the incidence

of side effects such as Horner’s syndrome and the advent of direct vision thoracoscopic techniques which can produce sympatholysis with a high degree of certainty [57, 59]. Further refinements of the technique of percutaneous lumbar sympatholysis have been claimed with the use of CT guidance [26, 85]. In theory, the needle

Figure 27.03A Approach to the lumbar sympathetic chain

Figure 27.03B Figure 27.02

Lumbar Sympathectomy

Lateral C-arm lumbar chemical sympathectomy

The Sympathetic Chain 443

tip can be placed onto the chain, avoiding adjacent structures such as the kidney and lung. The spread of contrast agent around the chain can be monitored and the operator assured of an adequate neurolysis. However, even with fast acquisition CT scanners, the technique is undoubtedly more cumbersome than chemical sympathectomy with a single needle technique under image intensifier control [40]. Alternatives to the use of phenol 10% in the treatment of peripheral vascular disease have been described including radiofrequency techniques, which are claimed to be as efficacious as phenol 6% [75]. However, it is the author’s experience that the discrete lesions produced by radiofrequency electrodes cannot provide the certainty of block provided by phenol 10%. More recently, retroperitoneoscopic surgical sympathectomy has been described for lower limb ischaemia where reconstructive surgery is not indicated. It has been claimed that retroperitoneoscopic lumbar sympathectomy successfully combines the advantages of minimally invasive surgery with the effectiveness of the open procedure [3]. Attempts have been made to critically evaluate the results of lumbar sympatholysis. In an earlier study, using digital plethysmographic techniques, Strandness concluded that lumbar sympathectomy does not alter the physiological response to calf muscle ischaemia and is probably of little use for claudication [99]. Cousins, in a study of the results

Figure 27.03B A-P C-arm lumbar chemical sympathectomy

of neurolytic sympathetic blockade, concluded that the technique is an effective method of relieving rest pain with a mean duration of sudomotor blockade of approximately 6 months [21]. A subsequent randomised prospective controlled trial supported Strandnsess’ earlier conclusion and chemical sympathectomy was not found to be beneficial in the treatment of intermittent claudication [23]. Cross suggested that chemical sympathectomy should be redefined as a pain relieving injection suitable for treating ischaemic rest pain, which is one of the major complaints of patients who are not suited to reconstructive surgery. Further prospective analysis has been conducted of CT-guided lumbar sympathectomy, which is proposed as an alternative to image intensifier guided blocks [41]. Criteria for success included doubling of the pre-interventional walking distance, the disappearance of rest pain, or the healing of ulcers. Approximately 50% of 83 patients in this study showed improvement. However, despite enhancing the ureters with intravenous contrast medium, two patients developed ureteric strictures probably due to injury from the neurolytic solution (alcohol 96%). Mention must be made of the treatment of Raynaud’s phenomenon and frostbite. Adson in 1929 wrote that “the striking, maintained, and unequivocal therapeutic effects of lumbar and dorsal sympathetic ganglionectomy in Raynaud’s disease seem to warrant the belief that surgical control in this disease is an accomplished fact” [2]. However, in a recent long-term retrospective study of thoracoscopic sympathectomy for Raynaud’s phenomenon, 34 patients underwent thoracoscopic sympathectomy and were assessed by questionnaire with a median time to follow-up of 40 months [101]. Despite an immediate beneficial effect seen in 83% of patients, symptoms recurred in 63%, gustatory sweating occurred in 30% and 43% regretted having the operation. These results might suggest that the surgical treatment of Raynaud’s disease is far from accomplished. Perhaps sympathectomy should be considered only as a salvage operation to limit progressive gangrene and ulceration [109]. Lastly, sympatholysis is thought to have a place in the treatment of frostbite — if performed early [97].

444 Philip FINCH

Sympatholysis in the Treatment of Abdominal Visceral Pain The treatment of abdominal cancer pain by sympathetic ablation procedures must be considered as one of the successful uses of this technique. Moore considers coeliac plexus blockade to be “the most effective, least hazardous means of palliative therapy for cancer of the upper intra-abdominal viscera” [69]. However, the role of coeliac plexus blockade for benign abdominal pain has never been well established [66]. Kappis introduced percutaneous splanchnic block in 1914, placing drugs posterior and superior to the diaphragmatic crura. As nociceptive afferents passing through the coeliac plexus run in the splanchnic nerves before reaching the sympathetic chain, this was a form of indirect coeliac plexus block [83]. An analogous situation is seen with the hypogastric plexus and nociceptive afferents arising in pelvic cancers. Lastly, blocks of the ganglion impar, which is the fused termination of the sympathetic chains, can be considered in the treatment of perineal pain states.

Figure 27.04

But first, the anatomy of the coeliac plexus and splanchnic nerves should be considered.

Anatomy of coeliac plexus The coeliac plexus has highly variable anatomy and is formed from the left and right coeliac ganglia. It surrounds the coeliac artery and the base of the superior mesenteric artery. The coeliac plexus lies anterolateral to the aorta and has considerable cephalocaudal variability [110]. It can be found level with the T12/L1 disc space to the middle of the vertebral body of L2. The left ganglia are typically located slightly caudal to the right.

Anatomy of splanchnic nerves The splanchnic nerves are considered to carry the majority of the upper abdominal visceral nociceptive afferents, especially those from the pancreas. They are therefore attractive as targets for nerve block or ablation techniques. The greater splanchnic nerve, which carries efferent preganglionic motor fibres and unmyelinated afferent sensory fibres, is usually formed by contributions from the T5 to T10 sympathetic ganglia. There is, like all matters

Splanchnic nerves

The Sympathetic Chain 445

Figure 27.05 Axial CT T11 – anatomy of adjacent structures

Figure 27.06A Axial L1 approach to coeliac plexus

concerning the sympathetic nervous system, considerable anatomical variability. The roots of the greater splanchnic nerve may vary in number from one to eight, four being the most common number [9]. The nerve runs obliquely over the ribs, approaching the spine and being more closely applied on the left. After piercing the diaphragm, the greater splanchnic nerve ends in the ipsilateral coeliac ganglion. The lesser splanchnic nerve is formed by rami from the ninth and tenth thoracic ganglia and passes through the diaphragm just inferior to the greater splanchnic nerve to reach the aorticorenal ganglion. The least splanchnic (T12) nerve is seldom seen in anatomical dissections. (Figure 27.04) A number of important structures lie in close proximity to the splanchnic nerves, which run caudally in a narrow compartment lateral to the vertebral bodies. The parietal pleura of the lung and the crura of the diaphragm form the lateral wall. (Figure 27.05)

Coeliac plexus blockade Many variations of this technique have been devised over the years, mainly for palliation of pancreatic cancer pain [117]. Neurolytic agents are deposited anterior to the aorta over at least two segments (L1 to L2). The various approaches have been compared and

Figure 27.06B

Sagital approach to coeliac plexus

found to give similar results [46]. Moore’s classical description includes a bilateral posterior approach as the ganglia are of course bilaterally represented [69]. Radiofrequency heat lesioning is not suited to the coeliac plexus due to its diffuse structure and usually quite substantial volumes of alcohol or phenol are used as a neurolytic agent. Radiological guidance includes C-arm fluoroscopy and CT. An anterior, per abdominal, approach can also be used with ultrasound or CT guidance. There are several advantages claimed for using CT guidance

446 Philip FINCH

studied at different stages of the disease [25]. Contrary to previous views, that neurolytic blocks should be retained to the end stages of the disease, the results would suggest that sympathetic plexus block should be considered earlier in the disease process rather than later.

Splanchnic nerve neurolysis

Figure 27.07A

Figure 27.07B

Coeliac plexus

Coeliac plexus

including increased accuracy in placement of the injection needle and the spread of neurolytic agent, which can be observed without the use of contrast medium [108]. (Figure 27.06A and Figure 27.06B, Figure 27.07A and Figure 27.07B) Coeliac plexus blockade has been the subject of several studies of efficacy and safety. There have been randomised controlled trials [45, 82, 116] and meta-analyses [29] that indicate that coeliac plexus neurolysis can provide long-lasting relief of cancer-related abdominal pain. Its use in the treatment of chronic benign abdominal pain is more controversial [66]. Side effects such as diarrhoea and hypotension are common and severe adverse effects such as paraplegia and retroperitoneal abscess are not unknown [1, 71]. Further, the use of neurolytic coeliac plexus blockade for abdominal cancer pain has been

Possibly a more precise method of blocking afferent pain sensations from upper abdominal viscera, splanchnic nerve neurolysis can be performed in a number of ways. The relatively predictable anatomy of the splanchnic nerves, especially their relationship to the vertebral bodies of T11 and T12, allow for precise needle placement using Carm fluoroscopy or CT [35, 83,]. (Figure 27.08A and Figure 27.08B) Curved blunt needles or radiofrequency cannulae can be introduced under oblique projection of the T11 or T12 vertebrae and by a vertebra-hugging technique advanced to the anterior one-third of the vertebral bodies as seen on lateral projection [32]. This technique avoids adjacent structures such as the lung base [31]. Blunt tips may well reduce the incidence of pleural or vascular puncture. Both posterior, transcrural and anterior per abdomen approaches have been described using CT guidance [67]. Direct thoracoscopic techniques can also be employed and perhaps provide even more certainty to neurolysis of the splanchnic nerves. Complications such as pneumothorax and diarrhoea are fortunately rare. Severe diaphragmatic paralysis has been described [89]. However, the use of alcohol in the chest is perhaps less well controlled than in the abdomen for coeliac plexus blockade. Few data exist on the efficacy of splanchnic blockade. Raj reported on 107 patients with 40% obtaining excellent pain relief with radiofrequency neurolysis [83]. Further trials are in progress and hopefully will support earlier encouraging preliminary data.

Hypogastric Plexus and Ganglion of Impar Neurolysis Some afferent pain sensations from the pelvic viscera pass through the superior hypogastric

The Sympathetic Chain 447

Figure 27.09 Figure 27.08A A A-P C-arm splanchnic nerve

Hypogastric plexus

structures just lateral to the plexus include the internal iliac vessels and the ureter. (Figure 27.09) Visceral pain probably originates in pelvic visceral nociceptors [18], but the existence of the nociceptors is controversial [8]. Visceral afferents pass without synapse to the dorsal horn mostly between levels T7 to L2. These visceral afferents are termed “sympathetic afferents”, but like the coeliac plexus there is disagreement as to whether they constitute part of the sympathetic nervous system, which is primarily efferent in its activity. There are a number of possible autonomic pathways that transmit pain sensation from the pelvis and not all of these pathways pass through the hypogastric plexus. This plexus is, however, reasonably accessible to nerve block techniques as opposed to the presacral plexus of nerves, and interruption of sympathetic pathways, including the superior hypogastric plexus, will provide pain relief.

Figure 27.08B

Lateral C-arm splanchnic nerve

plexus providing a target for neurolytic blockade. This is analogous to coeliac plexus blockade and in a similar fashion many different approaches have been considered since the first description of hypogastric plexus block by Plancarte [80]. The superior hypogastric plexus is situated on the anterior aspect of L5 to S1 disc and vertebral bodies and lies below the aortic bifurcation. Important

Neurolysis of the superior hypogastric plexus Attempts at denervation of pelvic sympathetic nerves date back to soon after the first description of the sympathetic chain [47, 93]. Subsequently, surgical presacral neurectomy was performed for severe dysmenorrhoea. Part of the superior hypogastric plexus was resected by various techniques and good pain relief reported in 70% of patients in one large retrospective series [6].

448 Philip FINCH

lie in a number of positions relative to the anterior surface of the coccyx [76].

Figure 27.10

Lateral C-arm hypogastric block

Plancarte described hypogastric plexus block for cancer pain using a blind (non-fluoroscopically controlled) bilateral posterior approach [80]. (Figure 27.10) However, this block can be difficult to perform with C-arm fluoroscopy due to the high angles of projection and the position of the pelvic crest. Alternative techniques have been devised, including a transdiscal [44, 102] and anterior (per abdomen) approach [50]. Additionally, CT guidance has been described and may assist positioning of the needle tip by both posterior [105] and anterior approaches [13]. Attempts at assessing efficacy have been limited. Plancarte and others reported on 227 cancer patients, with successful neurolysis occurring in 72% [81]. Also in a small series of patients blocked by the transdiscal route, good pain relief was reported in five of seven patients [30]. The use of superior hypogastric plexus block for benign pain has met with less success [8].

Ganglion of impar neurolysis The ganglion of impar, which is the fused caudal end of the sympathetic chain, lies over the ventral surface of the coccyx in the retroperitoneum. Once again, there is considerable anatomical variability in a sympathetic nervous system structure. It can

Blockade of the ganglion is described to relieve pain thought to be of sympathetic origin in the perineum, bladder, ureter, cervix and rectum [72, 111, 118]. What constitutes sympathetic as opposed to somatic pain in this region is, however, poorly described. Plancarte first described blockade of the ganglion impar for cancer pain [80]. He used a bent needle introduced between the coccyx and the rectum. A number of variations on this technique have subsequently been introduced including transsacrococcygeal ligament [111], cryoablation through the sacrococcygeal disc [70] and a paramedial approach [65]. These alternative approaches have attempted to reach this target without the attendant risks of puncture of the rectum. Few data are available on efficacy. Neurolysis of the ganglion impar has mainly been used for cancer pain, but it has also been described for sacral postherpetic neuralgia [65].

Cosmetic Indications for Sympathetic Neurolysis Severe primary hyperhidrosis and excessive facial blushing can cause such misery that patients seek surgical treatment in the form of sympathectomy. Often these patients are less than 30 years of age and complications, which can be significant, will affect their lives for many years. Excessive palmar sweating is currently treated with endoscopic thoracic sympathectomy (ETS) when conservative treatment fails – which is often the case. High success rates are claimed [74, 86]. Other forms of sympathetic chain ablation include the use of laser and radiofrequency heat. In the case of hyperhidrosis of the feet, some form of lumbar chain neurolysis is considered, usually including ganglia L2 to L4. Extensions of the indications for this technique have more recently included treatment of facial sweating and blushing. It is even advocated for social phobic disorders, which include fear of scrutiny, fear of performing in public, fear of eating with others because of trembling of the hands (coffee cup neurosis), excessive blushing, sweating, stuttering and trembling [95, 103]. Many would consider sympatholysis for these conditions to be

The Sympathetic Chain 449

a lifestyle procedure and similar in some ways to cosmetic aesthetic surgery [77]. Excessive palmar and axillary sweating can cause social embarrassment, especially in young adults. Certainly, excessive palmar sweating can cause great difficulties with writing, as documents become smeared. Plantar hyperhidrosis can also cause significant problems including cutaneous infections, trench foot, susceptibility to frostbite due to moisture accumulation and aesthetic problems due to sodden footwear [4]. Anatomy of the cervicothoracic chain The stellate ganglion is usually composed of both the inferior cervical and first thoracic ganglia. Sympathetic fibres to the cranium, and especially the eye, pass via the stellate ganglion and the cervical sympathetic chain, synapsing with postsganglionic fibres in the superior cervical ganglion. The stellate ganglion lies anterolateral to the body of the seventh cervical and lateral to the first thoracic vertebral bodies. There is marked anatomical variation in its position, as with all sympathetic nervous system structures [53]. (Figure 27.11) The position of the cervical sympathetic chain can also vary, lying within the carotid sheath in about 16% of cases in one cadaver study [63]. In the upper chest, the sympathetic chain lies more laterally, in

Figure 27.11

close approximation to the head and neck of each rib. On the left, the T2 ganglion lies adjacent to the aortic arch and in the second intercostal space. In about 16% of cases, the T3 ganglion is placed anterior to the third rib, making it inaccessible to direct posterior approaches for nerve block or radiofrequency lesioning. As it progresses caudally, the chain becomes more anterolateral to the vertebral bodies. This relationship is maintained into the lumbar region. (Figure 27.12, Figure 27.13A and Figure 27.13B)

Endoscopic thoracic sympathectomy Endoscopic thoracic sympathectomy (ETS) has become the preferred method of upper thoracic sympathectomy and was first described by Hughes in 1942 [43]. Kux subsequently described a large series in 1954 [56] and many authors have followed [42, 58, 119, 121]. In the last two decades, videoassisted fibre-optic endoscopy has vastly improved the operating conditions for this procedure. The main indication for ETS has been primary hyperhidrosis. Usually, the upper thoracic ganglia, including T2 and T3, are resected or destroyed by diathermy [14]. Sometimes T2 to T4 are included. Clipping is thought to offer some degree of reversibility [19] and confining the sympathectomy

Stellate ganglion anatomy

450 Philip FINCH

to T2 to T3 for facial sweating, T4 for palmar sweating and T5 for axillary sweating is thought to reduce undesirable sequelae [20].

Figure 27.12 Thoracic sympathetic chain

Figure 27.13A Stellate ganglion block – A-P C-arm

Figure 27.13B

Stellate ganglion block – Oblique C-arm

Alternative techniques for upper thoracic neurolysis include the use of neurolytic substances such as phenol, and radiofrequency thermolesioning. Despite the use of CT guidance, complications such as Horner’s syndrome and pneumothorax occur all too readily [27]. The use of radiofrequency (RF) thermolesioning offers a number of advantages, including the precise nature of the lesioning. There are some drawbacks with this method, as seen with the injection of neurolytic agents, including the development of pneumothorax. The use of curved blunt needles perhaps reduces the incidence of this complication [32, 119]. Radiofrequency lesioning has been described and popularised by Wilkinson [113, 114]. As with techniques for RF lesioning of the lumbar sympathetic chain, there is no easy method for determining the proximity of the RF electrode tip to the sympathetic chain. Direct endoscopic methods of lesioning the chain, largely overcome these difficulties as the ganglia are identified visually. (Figure 27.14A and Figure 27.14B) Complications of ETS can be significant in the short term including death, intrathoracic bleeding and anaesthetic complications [77]. In the longer term, compensatory hyperhidrosis is extremely common and has been recognised since 1933 [90]. Its rate of occurrence is reported to be as high as 67% [121] and even 94% [94]. The development of complications such as compensatory sweating can be accompanied by the development of significant psychological depression [38]. In some, this complication is sufficiently unpleasant for patients to request reversal of the surgery, if that is possible. Compensatory sweating develops more commonly in males and perhaps develops in all post-sympathectomy patients but is not perceived by all. It is therefore an inevitable not an optional side effect [94]! Gustatory sweating is also seen post-thoracic sympathectomy with profuse facial sweating after eating hot or spicy food. Its occurrence is reported in 47% of patients treated [121]. Horner’s syndrome, which can be facially disfiguring, is reported to occur in up to 3.8% of patients in one series [121]. Its incidence depends on the definition of the syndrome as a mild Horner’s syndrome may

The Sympathetic Chain 451

and Horner’s syndrome, which can even have medicolegal ramifications.

Sympathetic Blockade and Sympathectomy in the Treatment of Pain States

Figure 27.14A

Figure 27.14B

RF thoracic chain A-P C-arm

RF thoracic chain lateral C-arm

be marked by a miosis detectable only on close examination [77]. Other complications include cardiorespiratory effects and even rhinitis [42]. Endoscopic thoracic sympathectomy is considered to provide excellent results for patients with primary hyperhidrosis of the upper limb. Plantar sweating can also be relieved in nearly half of patients treated [74]. Quality of life measurements are improved by T4 ETS for upper limb hyperhidrosis [78]. However, a high initial patient satisfaction rate of 95.5% can become as low as 66.7% satisfied, at a mean of 14.6 years [42]. Although ETS is a minimally invasive and highly successful method of treating upper limb hyperhidrosis, these comments must be weighed against the possibility of significant long-term side effects, especially compensatory sweating

Sympathetic blockade had long been considered a mainstay of treatment for neuropathic pain states, especially complex regional pain syndrome (CRPS), types I and II [7]. Surgical sympathectomy has also been considered the treatment of choice for severe burning pain states arising out of nerve injuries in wartime. The supporting evidence for such treatment is however lacking. Early, more rational, use of surgical sympathectomy appeared with the work of René Leriche during World War I [10, 62]. Subsequent wartime experience entrenched sympathectomy as the most effective means of treating causalgia, a term devised by Silas Weir Mitchell during the American Civil War (1864). Further experience in World War II and data collected from American and British forces led to statements that “one of the outstanding surgical lessons that was learned during World War II was that interruption of the appropriate sympathetic nerve fibres is almost invariably effective in the treatment of causalgia” [87]. Long-term studies of such efficacy are sadly lacking and of course the conduct of a randomised controlled trial in war would be difficult, if not impossible. Similar symptoms and signs, including burning pain coupled with autonomic features were subsequently labelled reflex sympathetic dystrophy, among many other terms, and were thought to arise from aberrations of the sympathetic nervous system, but without nerve injury. In an attempt to get away from such a mechanistic term that perhaps implied a pathophysiological mechanism, a new taxonomy (CRPS I and II) was devised in 1995 [98]. The original International Association for the Study of Pain criteria were further refined by Hardin et al. [11]. There was subsequently a realisation that both CRPS I and II were part of a clinical continuum of disorders which may have a common aetiology [49]. In the new classification, the syndrome was described as sympathetically maintained pain (SMP) if it responded to sympathetic blockade. If it

452 Philip FINCH

did not respond, it was described as sympathetically independent pain (SIP). This dichotomy of terms also suggests a pathophysiological mechanism. The involvement of the sympathetic nervous system in causalgia and reflex sympathetic dystrophy, which forms the rationale for treatment by sympathetic interruption, has been increasingly questioned [12]. In a recent Cochrane collaborative review, Cepeda and others determined that there have only been two randomised controlled trials of local anaesthetic sympathetic blockade for CRPS worthy of consideration [16]. They reviewed the likelihood of sympathetic blockade providing pain relief in CRPS, the persistence of benefits and the incidence of side effects. Their conclusions were sobering, to say the least. They could make no conclusion concerning the effectiveness of sympathetic blockade, the duration of pain relief could not be estimated, if any, and lastly, the lack of data on complications, despite the invasive nature of such blocks, perhaps suggested under-reporting [16]. Cepeda and others in an earlier study indicated that sympathetic blockade was advocated mainly on the basis of weak evidence culled from case series and that only about one-third of patients obtained full pain relief [17]. All practising pain physicians have witnessed almost magical responses of patients with CRPS to sympathetic blockade. It is possible that these responses may simply be due to powerful, active placebo effect and further study is required [5, 36]. Surgical sympathectomy has also come under closer scrutiny. In an extensive and systematic literature review, it was noted that a high proportion of patients undergoing upper or lower limb surgical sympathectomy had this procedure for primary hyperhidrosis (84%). A smaller proportion (2.7%) underwent sympathectomy for pain states. No controlled trials were found and complications were three time higher for those undergoing treatment for pain states [34]. The potentially disabling complications that can accompany surgical sympathectomy have been mentioned earlier in this chapter. The same authors conducted a Cochrane collaborative review in 2002 and concluded that “the practice of surgical and chemical sympathectomy is based on poor quality evidence, uncontrolled studies and personal experience. Furthermore, complications of the procedure may be significant, in terms of both worsening the pain or producing a

new pain syndrome” [64]. In essence, the practice of sympathectomy for treating neuropathic pain is based on very weak evidence. Careful placebo controlled studies of local anaesthetic sympathetic blockade and neurolysis in the treatment of CRPS I and II should be strongly considered. Otherwise, we as pain physicians risk losing the support of our colleagues, regulatory authorities and patients alike.

Conclusion Although still widely used in several fields of medicine, both sympathetic blockade and sympathectomy have limited efficacy and potential for good. Despite initial enthusiasm, the last decade of the 20th century has seen the emergence of trial data which have demonstrated the limitations of these techniques. Undoubted success can be seen in the area of cancer pain; both in the use of diagnostic sympathetic blockade with local anaesthetic agents and in the longer-term treatment of cancer pain with neurolytic substances. This success is also seen to some extent in peripheral vascular disease. However, in the area of cosmetic sympathectomy for primary hyperhidrosis and in the treatment of neuropathic pain syndromes, such as CRPS, the techniques are perhaps over-utilised and one might even say that they have the potential for abuse for financial gain. It is hard to argue for multiple sequential local anaesthetic sympathetic blocks for CRPS when so few patients respond. Further, the use of sympathetic blockade may be based on a flawed premise of autonomic efferent activity. In the case of sympathectomy for hyperhidrosis, sympathetic chain ablation has the potential for replacing one devastating set of symptoms with another set that are equally devastating and long lasting. How should we address this dilemma? First of all, the active placebo effect must be studied, especially in the area of treatment of CRPS. More recent evidence would suggest that this condition may have an aberration of central nervous system pain processing as a basis for its pathogenesis. The active placebo can have powerful central effects and careful allowance for this phenomenon must be made in any future trials of efficacy of sympathetic blockade.

The Sympathetic Chain 453

As a better understanding of the role of the sympathetic chain is gained, then more refined surgical techniques may be devised that can minimise the rate of undesirable sequelae. Finally, visceral cancer pain sufferers will continue to gain excellent pain relief from targeted blocks allowing a reduction in centrally acting drugs that can cause sedation and confusion. However, even this successful use of sympathetic blockade needs further refinement and review. Improvements in patient selection, the use of sympathetic blockade earlier in the course of the disease and better target identification will cement its place in the spectrum of treatment techniques in pain medicine.

Summary •

Both sympathetic blockade and sympathectomy have limited efficacy in the

• •

• •

•

treatment of pain syndromes. The variable anatomy of the sympathetic chain produces unpredictable results in sympathetic pain management techniques. Historically, specific techniques have been developed for four main areas of interest: the cervicothoracic ganglia, the splanchnic-coeliac plexus, the lumbar ganglia and the superior hypogastric plexus. The use of these techniques for the treatment of cancer pain, and to some extent in peripheral vascular disease, is undoubtedly successful. However, none of the techniques described is consistently successful in the treatment of primary hyperhidrosis or neuropathic pain syndrome such as CRPS. Improvement in both technique and patient selection may advance these treatments in the management of sympathetic pain.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

11. 12. 13. 14. 15. 16. 17. 18.

Abdalla EK, Schell S. Paraplegia following intraoperative celiac plexus injection. J Gastrointest Surg 1999;3:668–71. Adson A, Brown G. The treatment of Raynaud’s disease by resection of the upper thoracic and lumbar sympathetic ganglia and trunks. Surg Gynecol Obstet 1929;XLVIII:577–603. Beglaibter N, Berlatzky Y, Zamir O, et al. Retroperitoneoscopic lumbar sympathectomy. J Vasc Surg 2002;35:815–7. Benohanian A, Dansereau A, Bolduc C, et al. Localized hyperhidrosis treated with aluminum chloride in a salicylic acid gel base. Int J Dermatol 1998;37:701–3. Benson H, Friedman R. Harnessing the power of the placebo effect and renaming it “remembered wellness”. Annu Rev Med 1996;47:193–9. Black W. Use of presacral sympathectomy in treatment of dysmenorrhea. HYPERLINK “http://journals.elsevierhealth. com/periodicals/ymob” Am J Obstet Gynecol 1964;89:16. Bonica J. Causalgia and other reflex sympathetic dystrophies. In Bonica J, ed. The Management of Pain, 2nd edn. Philadelphia: Lea & Febiger, 1990:220–43. Bosscher H. Blockade of the superior hypogastric plexus block for visceral pelvic pain. Pain Practice 2001;1:162–70. Bradley E, Bem J. Nerve blocks and neuroablative surgery for chronic pancreatitis. World J Surg 2003;27:1241–8. Breivik H, Cousins M, Lofstrom J. Sympathetic neural blockade of upper and lower extremity. In Cousins M, Bridenbaugh P, eds. Neural Blockade in Clinical Anesthesia and Management of Pain, 3rd edn. Philadelphia: LippincottRaven, 1998:411–47. Bruehl S, Harden R, Galer B, et al. External validation of IASP diagnostic criteria for complex regional pain syndrome and proposed research diagnostic criteria. Pain 1999;81:147–54. Campbell J, Raja S. Reflex sympathetic dystrophy. Neurology 1995;45:1235–7. Cariati M, De Martini G, Pretolesi F, et al. CT-guided superior hypogastric plexus block. J Comput Assist Tomogr 2002;26:428–31. Cartier B, Cartier P. Thoracoscopic cervicodorsal sympathectomy with diathermy. Ann Vasc Surg 1999;13:582–5. Casale R, Elam M. Normal sympathetic nerve activity in a reflex sympathetic dystrophy with marked skin vasoconstriction. J Auton Nerv Syst 1992;41:215–20. Cepeda M, Carr D, Lau J. Local anesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev 2005;4:1–9. Cepeda M, Lau J, Carr D. Defining the therapeutic role of local anesthetic sympathetic blockade in complex regional pain syndrome: A narrative and systematic review. Clin J Pain 2002;18:216–33. Cervero F, Laird J. Visceral pain. Lancet 1999;353: 2145–8.

454 Philip FINCH

19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48.

49. 50.

Chen SC, Lin CY, Chou MC, et al. Endoscopic thoracic sympathetic block by clipping for recurrent palmar hyperhidrosis. Int Surg 2005;90:284–8. Chou S, Kao E, Lin C, et al. The importance of classification in sympathetic surgery and a proposed mechanism for compensatory hyperhidrosis: Experience with 464 cases. Surg Endosc 2006;20:1749–53. Cousins M, Reeve T, Walsh J, et al. Neurolytic lumbar sympathetic blockade: Duration of denervation and relief of rest pain. Anaesth Intensive Care 1979;7:121–35. Cowley R, Yeager G. Anatomic observations on the lumbar sympathetic nervous system. Surgery 1949;25:880. Cross F, Cotton L. Chemical lumbar sympathectomy for ischemic rest pain: A randomized, prospective controlled clinical trail. Am J Surg 1985;150:341–5. de Leon-Casasola O. Critical evaluation of chemical neurolysis of the sympathetic axis for cancer pain. Cancer Control 2000; 7:142–8. de Oliveira R, dos Reis M, Prado W. The effects of early or late neurolytic sympathetic plexus block on the management of abdominal or pelvic cancer pain. Pain 2004;110:400–8. Dondelinger R, Kurdziel J. Percutaneous phenol neurolysis of the lumbar sympathetic chain with computed tomography control. Ann Radiol (Paris) 1984;27:376–9. Dondelinger R, Kurdziel J. Percutaneous phenol block of the upper thoracic sympathetic chain with computed tomography guidance: A new technique. Acta Radiol 1987;28:511–5. Drummond P, Finch P. Persistence of pain induced by startle and forehead cooling after sympathetic blockade in patients with complex regional pain syndrome. J Neurol Neurosurg Psychiatry 2004;75:98–102. Eisenberg E, Carr D, Chalmers T. Neurolytic celiac plexus block for treatment of cancer pain: A meta-analysis. Anesth Analg 1995;80:290–5. Erdine S. Transdiscal approach to the superior hypogastric plexus. Medicine Grand Rounds; 2000 June; Lubbock, Texas: Texas Tech University Health Sciences Center. Finch P. Sympathetic neurolysis. In Prithvi Raj P, ed. Textbook of Regional Anesthesia. New York: Churchill Livingstone, 2002:667–85. Finch P, Racz G, McDaniel K. A curved approach to nerve blocks and radiofrequency lesioning. Pain Digest 1997;7:251–7. Freeman N. The treatment of causalgia arising from gunshot wounds of the peripheral nerves. Surgery 1947;22:68– 92. Furlan A, Mailis A, Papagapiou M. Are we paying a high price for surgical sympathectomy?: A systematic literature review of late complications. ISIS Scientific Newsletter 2001;4:17–37. Garcea G, Thomasset S, Berry D, et al. Percutaneous splanchnic nerve radiofrequency ablation for chronic abdominal pain. Aust N Z J Surg 2005;75:640–4. Gotzsche P. Is there logic in the placebo? Lancet 1994;344:925–6. Hanningto-Kiff J. Sympathetic nerve blocks in painful limb disorders. In Wall P, Melzack R, eds. Textbook of Pain, 3rd edn. Edinburgh: Churchill Livingstone, 1994:1035–52. Hashim N, Wilson N. Depression accompanying compensatory hyperhidrosis following endoscopic thoracic sympathectomy. Clin Exp Dermatol 2006;31:818–9. Hassantash S, Maier R, Kaiser L, et al. Sympathectomy for causalgia: Experience with military injuries. J Trauma 2000;49:266–71. Hatandgi V, Boas R. Lumbar sympathectomy: A single needle technique. Br J Anaesth 1985;57:285–9. Heindel W, Ernst S, Manshausen G, et al. CT-guided lumbar sympathectomy: Results and analysis of factors influencing the outcome. Cardiovasc Intervent Radiol 1998;21:319–23. Herbst F, Plas E, Fugger R, et al. Endoscopic thoracic sympathectomy for primary hyperhidrosis of the upper limbs : A critical analysis and long-term results of 480 operations. Ann Surg 1994;220:86–90. Hughes J. Endothoracic sympathectomy. Proc R Soc Med 1942;35:585–6. Ina H, Kitoh T. A new approach to superior hypogastric nerve block: Transvertebral disk L5–S1 technique. Reg Anesth 1992;17:123. Ischia S, Ischia A, Polati E, et al. Three posterior percutaneous celiac plexus block techniques: A prospective, randomized study in 61 patients with pancreatic cancer pain. Anesthesiology 1992;76:534–40. Ischia S, Polati E, Finco G, et al. Celiac block for the treatment of pancreatic pain. Curr Rev Pain 2000;4:127–33. Jaboulay M. Le traitment de la nevralgie pelviene par paralyse due sympathique sacre. Lyon Medical 1899;90:102. Jadad A, Carroll D, Glynn C, et al. Intravenous regional sympathetic blockade for pain relief in reflex sympathetic dystrophy: A systematic review and a randomized, double-blind crossover study. J Pain Symptom Manage 1995;10:13– 20. Janig W. The puzzle of reflex sympathetic dystrophy: Mechanisms, hypothesis, open questions. In Janig W, StantonHicks M, eds. Reflex Sympathetic Dystrophy: A Reappraisal. Seattle: IASP Press, 1996:1–24. Kanazi G, Perkins F, Thakur R, et al. New technique for superior hypogastric plexus block. Reg Anesth Pain Med 1999;24:473–6.

The Sympathetic Chain 455

51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83.

Kapural L, Mekhail N. Assessment of sympathetic blocks. Tech Reg Anesth Pain Manage 2001;5:82–7. Kargar S, Yasini M, Ayatollahi V. Thoracic sympathectomy in social phobia: A pilot study. Internet J Surg 2006;7. Katritsis ED, Lykaki-Anastopoulou G, Papadopoulos N. The relations of the superior pole of the stellate ganglion to the vertebral artery. Anat Anz 1981;150:259–63. Koman L, Smith B, Pollock FJ, et al. The microcirculatory effects of peripheral sympathectomy. J Hand Surg 1995;20A:709–17. Kotzareff A. Resection partielle de tronc sympathetique cervical droit pour hyperhidrose unilaterale. Rev Med Suisse Romande 1920;40:111–3. Kux E. Thorakoskopische Eingriffe am Nervensystem. Stuttgart: Gerog Thieme Verlag, 1954. Kux M. Thoracic endoscopic sympathectomy in palmar and axillary hyperhidrosis. Arch Surg 1978;113:264–6. Kwong K, Cooper L, Bennett L, et al. Clinical experience in 397 consecutive thoracoscopic sympathectomies. Ann Thorac Surg 2005;80:1063–6. Lee A, Agarwal S, Sadhu D. A 7-year experience with thoracoscopic sympathectomy for critical upper limb ischemia. World J Surg 2006;30:1644–7. Leriche R. De le longation et de la section des nerfs perivasculaires dans certains syndromes douloureux d’origine arterielle et dans quelques troubles trophiques. Lyon Chirurgical 1913;X:378. Leriche R. De la causalgie envisagée comme une névrite du sympathique et de son traitement par la dénudation et l’excision des plexus nerveux péri-arteriels. La Presse Médicale 1916;24:178–280. Leriche R. The Surgery of Pain. London: Bailliere, Tindall and Cox, 1939. Lyons A, Mills C. Anatomical variants of the cervical sympathetic chain to be considered during neck dissection. Br J Oral Maxillofac Surg 1998;36:180–2. Mailis-Gagnon A, Furlan A. Sympathectomy for neuropathic pain. Cochrane Database Syst Rev 2002;1:1–18. McAllister R, Carpentier B, Malkuch G. Sacral postherpetic neuralgia and successful treatment using a paramedial approach to the ganglion impar. Anesthesiology 2004;101:1472–4. McKay W, McKay R. Neurolytic celiac plexus block for benign pain: Still a question? Reg Anesth Pain Med 2003;28:495– 7. Mercadante S, La Rosa S, Villari P. CT-guided neurolytic splanchnic nerve block by an anterior approach. J Pain Symptom Manage 2002;23:268–70. Mitchell S, Moorehouse G, Keen W. Gunshot Wounds and Other Injuries of Nerves. Philadelphia: JB Lippincott, 1864. Moore D. Celiac (splanchnic) plexus block with alcohol for cancer pain of the upper intra-abdominal viscera. In Bonica J, Ventafridda V, eds. Advances in Pain Research and Therapy. New York: Raven Press, 1979:357–71. Munir M, Zhang J, Ahmad M. A modified needle-inside-needle technique for the ganglion impar block. Can J Anaesth 2004;51:915–7. Navarro-Martinez J, Montes A, Comps O, et al. Retroperitoneal abscess after neurolytic celiac plexus block from the anterior approach. Reg Anesth Pain Med 2003;28:640–4. Nebab E, Florence I. An alternative needle geometry for interruption of the ganglion impar. Anesthesiology 1997;86:1213–4. Neumayer C, Bischof R, Fugger M, et al. Efficacy and safety of thoracoscopic sympathicotomy for hyperhidrosis of the upper limb: Results of 734 sympathicotomies. Ann Chir Gynaecol 2001;90:195–9. Neumayer C, Panhofer P, Zacherl J, et al. Effect of endoscopic thoracic sympathetic block on plantar hyperhidrosis. Arch Surg 2005;140:676–80. Noe C, Haynsworth R. Lumbar radiofrequency sympatholysis. J Vasc Surg 1993;17:801–6. Oh C, Chung I, Ji H, et al. Clinical implications of topographic anatomy on the ganglion impar. Anesthesiology 2004;101:249–50. Ojimba T, Cameron A. Drawbacks of endoscopic thoracic sympathectomy. Br J Surg 2004;91:264–9. Panhofer P, Zacherl J, Jakesz R, et al. Improved quality of life after sympathetic block for upper limb hyperhidrosis. Br J Surg 2006; 93:582–6. Perlow S, Vehe K. Variations in the gross anatomy of the stellate and lumbar sympathetic ganglia. Am J Surg 1935;30:454. Plancarte R, Amescua C, Patt R, et al. Superior hypogastric plexus block for pelvic cancer pain. Anaesthesiology 1990;73:236–9. Plancarte R, de Leon-Casasola O, El-Helaly M, et al. Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer. Reg Anesth 1997;22:562–8. Polati E, Finco G, Gottin L, et al. Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 1998;85:199–201. Raj P, Thomas J, Heavner J, et al. The development of a technique for radiofrequency lesioning of splanchnic nerves. Curr Rev Pain 1999;3:377–87.

456 Philip FINCH

84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119.

Raj PP, ed. Textbook of Regional Anesthesia. New York: Churchill Livingstone, 2002. Redman D, Robinson P, Al-Kutoubi M. Computerised tomography guided lumbar sympathectomy. Anaesthesia 1986; 41:39–41. Reisfeld R, Nguyen R, Pnini A. Endoscopic thoracic sympathectomy for hyperhidrosis: Experience with both cauterization and clamping methods. Surg Laparosc Endosc Percutan Tech 2002;12:255–67. Richards R. Causalgia: A centennial review. Arch Neurol 1967;16:339–50. Rocco A, Palombi D, Raeke D. Anatomy of the lumbar sympathetic chain. Reg Anesth 1995;20:13–9. Rosenthal J. Diaphragmatic paralysis complicating alcohol splanchnic nerve block. Anesth Analg 1998;6:845–6. Ross J. Sympathectomy as an experiment in human physiology. Br J Surg 1933;21:5–19. Royle N. The treatment of spastic paralysis by sympathetic ramisection. Surg Gynecol Obstet 1924;XXXIX:701–20. Royle N. The surgical treatment of Raynaud’s disease and similar conditions. Med J Aust 1927;XI(Suppl.):341–3. Ruggi G. Sympathectomia al collo ed ale abdome. Policlinoico 1899:103. Schick C, Horbach T. Sequelae of endoscopic sympathetic block. Clin Auton Res 2003;13(Supp1):136–9. Scholing A, Emmelkamp P. Treatment of fear of blushing, sweating, or trembling. Results at long-term follow-up. Behav Modif 1996;20:338–56. Schott G. Interrupting the sympathetic outflow in causalgia and reflex sympathetic dystrophy. BMJ 1998;316:792– 3. Shumacker H, Kilman J. Sympathectomy in the treatment of frostbite. Arch Surg 1964;89:575–84. Stanton-Hicks M, Janig W, Hassenbusch S, et al. Reflex sympathetic dystrophy: Changing concepts and taxonomy. Pain 1995;63:127–33. Strandness D, Bell J. Critical evaluation of the results of lumbar sympathectomy. Ann Surg 1963;160:1021–9. Telaranta T. Treatment of social phobia by endoscopic thoracic sympathicotomy. Eur J Surg 1998;164(Suppl 580):27– 32. Thune T, Ladegaard L, Licht P. Thoracoscopic sympathectomy for Raynaud’s phenomenon: A long-term follow-up study. Eur J Vasc Endovasc Surg 2006;32:198–202. Turker G, Basagan-Mogol E, Gurbet A, et al. A new technique for superior hypogastric plexus block: The posteromedian transdiscal approach. Tohoku J Exp Med 2005;206:277–81. Uhde T, Tancer M, Black B, et al. Phenomenology and neurobiology of social phobia: Comparison with panic disorder. J Clin Psychiat 1991;52(Suppl):31–40. Umeda S, Arai T, Halano Y, et al. Cadaver anatomic analysis of the best site for chemical lumbar sympathectomy. Anesth Analg 1987;66:643–6. Waldman S, Wilson W. Superior hypogastric plexus block using a single needle and computed tomographic guidance: Description of a modified technique. Reg Anesth 1991;16:286–7. Waldman SD, ed. Interventional Pain Management, 2nd edn. Philadelphia: WB Saunders, 2001. Wallin B, Torebjork H, Hallin R. Preliminary observations on the pathophysiology of hyperalgesia in the causalgic pain syndrome. In Zotterman Y, ed. Sensory Function of the Skin. New York: Pergamon, 1976:489–99. Wang P, Shang M, Qian Z, et al. CT-guided percutaneous neurolytic celiac plexus block technique. Abdom Imaging 2006; 31:710-8. Wang W, Lai C, Chang K, et al. Peripheral sympathectomy for Raynaud’s phenomenon: A salvage procedure. Kaohsiung J Med Sci 2006;22:491–9. Ward E, Rorie D, Nauss L, et al. The celiac ganglia in man: Normal anatomic variations. Anesth Analg 1979;58:461– 5. Wemm K, Saberski L. Modified approach to block the ganglion impar (ganglion of Walther). Reg Anesth 1995;20:544– 5. Weyland A, Weyland W, Carduck H, et al. Which paravertebral approach is optimal for lumbar sympathetic blocks? Results of computer tomographic simulation studies. Pain 1990;5(Suppl):489. Wilkinson H. Stereotactic radiofrequency sympathectomy. Pain Clinic 1995;8:107–15. Wilkinson H. Percutaneous radiofrequency upper thoracic sympathectomy. Neurosurgery 1996;38:715–25. Williams P, ed. Gray’s Anatomy, 38th edn. New York: Churchill Livingstone, 1995:1297,1303–4,1793. Wong G, Schroeder D, Carns P, et al. Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: A randomized controlled trial. JAMA 2004;291:1092–9. Yamamuro M, Kusaka K, Kato M, et al. Celiac plexus block in cancer pain management. Tohoku J Exp Med 2000;192:1–18. Yeo S, Chong J. A case report on the treatment of intractable anal pain from metastatic carcinoma of the cervix. Ann Acad Med Singapore 2001; 30:632–3. Yilmaz E, Dur A, Cuesta M, et al. Endoscopic versus transaxillary thoracic sympathectomy for primary axillary and palmar hyperhidrosis and/or facial blushing: 5-year experience. Eur J Cardiothorac Surg 1996;10:168–72.

The Sympathetic Chain 457

120. Yin W. Posterior parasagittal approach to thoracic paravertebral neural structures with curved cannulae: Methodology and technique to decrease the incidence of unintentional visceral injury with thoracic percutaneous approaches for the treatment of chronic pain. ISIS Scientific Newsletter 2000;4:18–40. 121. Zacherl J, Huber E, Imhof M, et al. Long-term results of 630 thoracoscopic sympathicotomies for primary hyperhidrosis: The Vienna experience. Eur J Surg 1998;(Suppl 580):43–6.

28

Kai On SUN, Henry Ka Fai TONG

Interventional Procedures for Back and Neck Pain

Introduction

INTRODUCTION EPIDURAL STEROID INJECTION SLEEVE ROOT INJECTION FACET JOINT SYNDROME AND ITS INTERVENTION SACROILIAC JOINT PAIN AND ITS INTERVENTION DISCOGENIC BACK PAIN AND ITS INTERVENTION EPIDUROSCOPY AND EPIDUROLYSIS

Both neck and back pain are very common complaints in many communities. More than half of the population in the United States suffers from low back pain at some time; the annual incidence is at least 5%. Back pain incapacitates up to 20% of workers for long period (>4 weeks), absorbs 41% of the cost of workers’ compensation and costs society more than $15 million each year [1, 7, 24]. A similar situation exists elsewhere, including Hong Kong [26]. However, the cause can be very diverse, ranging from simple neck and back sprain to some less well-known causes such as facet joint arthritis and sacroiliitis. Although 90% of low back pain resolves after 6 weeks and another 5% after 12 weeks, about 5% will advance from an acute to a chronic condition, if we ignore the patient’s complaints. Without proper care, some patients will progress to chronic back or neck pain. In order to determine the true pathology of the patient’s symptoms, it is necessary to take a proper history and examine meticulously to find the underlying mechanisms of pain production. Sometimes, more than one pain generator can be present in the same patient. Referred pain should also be excluded before a definitive diagnosis is made. For example, renal or aortic pathology can also give rise to symptoms similar to low back pain. This chapter will discuss the interventional management of back and neck pain associated with skeletal causes. Pain related to muscle conditions are discussed in Chapter 14. Once the underlying pathophysiology is found, appropriate intervention can take place to alleviate the patient’s suffering.

VERTEBROPLASTY AND KYPHOPLASTY

Epidural Steroid Injection CONCLUSION REFERENCES

Epidural steroid injection has been used for back pain caused by annulus tear, chronic lumbar degenerative disc disease,

460 Kai On SUN, Henry Ka Fai TONG

herniated nucleus pulposus without neurological deficits and herniated nucleus pulposus with nerve root irritation or compression. It has also been used for pain caused by degenerative joint disease, spondylosis, scoliosis, spondylolisthesis, post-laminectomy syndrome and spinal stenosis. A favourable response has been reported in patients with an advanced educational background, a primary diagnosis of radiculopathy and pain of less than 6 months’ duration. Factors associated with poor outcome include constant pain, frequent sleep disruption and being unemployed owing to pain [29]. Despite the use of epidural steroid injection for the clinical conditions listed above, its efficacy varies. The most favourable clinical predictor of good response is the presence of radiculopathy in patients with back pain because of the anti-inflammatory effects of corticosteroid on compressed and/or inflamed nerve roots. The rationale for epidural steroids focuses on their strong anti-inflammatory action. Nerve root oedema is seen in patients with herniated discs. Herniated disc have been found to contain high levels of the enzyme phospholipase A2, which liberates arachidonic acid from cell membranes. Steroids work by interfering with the inflammatory process. Furthermore, administration of epidural solutions clears or dilutes the chemical irritants. Steroids also exert their effects in other ways, including membrane stabilisation, inhibition of neural peptide synthesis or action, suppression of ongoing neuronal discharge and suppression of the sensitisation of the dorsal horn neurons. The most common steroids used in the epidural space include methylprednisolone acetate 80 mg and triamcinolone diacetate 50 mg. In general, a total volume of 6 to 10 ml is adequate for lumbar epidural administration, whereas 4 to 6 ml is used for the cervical region. Larger volumes of 15 to 30 ml are required for administration through the caudal space. In contrast, only 0.5 to 2 ml is used for transforaminal injections. The objective of epidural steroid injection is to deliver corticosteroid close to the site of pathology, presumably onto an inflamed nerve root. The epidural space can be accessed through various approaches: the interlaminar approach, caudal approach and transforaminal approach. Caudal and interlaminar epidural injections are affected by the presence or absence of epidural ligaments

or scarring, which may prevent migration of the posteriorly administered injectate to the anterior epidural space. For optimum results, the corticosteroid should reach the ventral epidural space in front of the dural sac and behind the disc. The transforaminal approach shows good ventral flow, whereas the interlaminar method predominantly shows dorsal flow, which is far removed from the usual site of inflammation. The response of the patient determines whether repeated injections are required. It is preferable to wait at least 2 weeks between injections. If the patient has an excellent response, the epidural steroid injection can be repeated on an as-needed basis if the pain returns. If the patient has minimal relief with the interlaminar epidural injection, one transforaminal, site-specific, epidural steroid injection may be tried. The epidural steroid injection can be repeated every 3 months (maximum three times per year) only if the patient gets at least 50% relief for at least 6 weeks. The interlaminar approach carries the disadvantages of diluting the injectate, extra-epidural or intravascular placement of the needle, preferential cranial flow of the solution and preferential posterior flow of the solution, technical difficulties in postsurgical patients, dural puncture and trauma to the spinal cord. The transforaminal epidural injections carry the potential complications of intraneural injection, neural trauma, intravascular injection and spinal cord trauma. Other complications of epidural steroid administration include inadvertent intrathecal steroid injection causing aseptic meningitis, adhesive arachnoiditis, pachymeningitis, or conus medullaris syndrome. Epidural steroids affect the hypothalamuspituitary-adrenal axis, resulting in depression of the plasma cortisol levels for up to 3 to 5 weeks [3]. They can also cause iatrogenic Cushing’s syndrome, congestive heart failure secondary to fluid retention and changes in blood glucose levels in susceptible individuals. Fortunately, these side effects are uncommon. Most of the side effects reported are minor and transient [22] and are related to systemic absorption; they include insomnia, rash and pruritus. The caudal epidural technique is useful in the treatment of a variety of chronic benign pain syndromes, including lumbar radiculopathy, spinal stenosis and post-laminectomy syndrome.

Interventional Procedures for Back and Neck Pain 461

Because of the simplicity and safety associated with the caudal approach to the epidural space, this technique is replacing the lumbar epidural approach for these indications in some pain centres. The caudal approach to the epidural space is especially useful in patients who have previously undergone low back surgery, which may make the lumbar approach to the epidural space less efficacious. The caudal approach to the epidural space may be used in the presence of anticoagulation or coagulopathy, so local anaesthetics, opioids and steroids can be administered via this route even when spinal or lumbar epidural approaches are contraindicated. Potential risk of haematogenous spread via the venous plexus, local infection and sepsis are the only absolute contraindications to the caudal approach to the epidural space. In a recent review, there is limited evidence that epidural steroid alone benefits the symptoms of sciatica, either the condition alone or associated with low back pain, in the short to intermediate term (level 3) [4]. There is also limited evidence that epidural steroid injection alone does not affect the long-term prognosis of sciatica (level 3). The caudal epidural injection of steroid with local anaesthetic benefits pain and function in low back pain in the intermediate term (level 3).

Sleeve Root Injection Just as discogenic pain can be studied by careful blocks of the intervertebral disc, so too the central neural elements can be investigated logically and sequentially. The nerve root sleeve is particularly accessible to precise local anaesthetic blocks. Segmental information gained from such nerve root blocks can be helpful in sorting out confusing patterns of referred pain to the limbs. This may be beneficial to those patients with contraindications to neuraxial block. There are some regional differences in the approach to each area of the spine, however, partly as a result of the proximity of structures, such as the lung or vertebral artery. Injectate volumes must be restricted to 1 ml; a larger volume would ensure spread to adjacent nerve roots via the epidural space, resulting in loss of segmental specificity. Only the lumbar and sacral nerve root sleeve injection will be discussed here.

Numerous publications have discussed the anatomy and approach to the lumbar nerve root sleeve [14, 16, 18]. Kikuchi and associates [17] have described the anatomic variants of the dorsal root ganglia, and Derby and colleagues [10] have reviewed the techniques of blocking the lumbar nerve root sleeve. In general, the principles of approach to these neural structures are little different from those of the cervical approach. To avoid impalement of the nerve root, the needle tip is directed to lie just inferior to the midpoint of the pedicle. This can be achieved by first aligning the fluoroscopy beam to pass squarely through the disc space. For the lumbosacral disc, a considerable degree of cranial angulation may be required. The C-arm of the fluoroscope is then rotated to an oblique position so that the edges of the facet joint become clearly defined. A spinal needle with a curve in the terminal portion is then passed down the fluoroscopy beam to strike the inferior margin of the pedicle without contacting the nerve root. Derby and colleagues [10] describe this as the “6 o’clock position”, with the oblique view of the pedicle representing the clock face. Small volumes of contrast and local anaesthetic agents are then gently injected. If an electrically insulated needle is used to approach the nerve root, electrical stimulation can also be used to study patterns of referral to the lower limbs. Sacral nerve roots can easily be accessed by passing a spinal needle through the appropriate posterior sacral foramen. This route of access is visualised by adjusting the fluoroscopy beam to align the round posterior foramen with the curvilinear marking of the anterior foramen. The needle is passed through the epidural space onto the peripheral nerve at a point just anterior to the anterior sacral plate. Injection of contrast agents is best performed under direct fluoroscopic guidance because veins are easily entered in the vicinity of the sacral nerve roots and can lead to false-negative block.

Facet Joint Syndrome Approximately 15–40% of low back pain is due to dysfunction or inflammation of the facet (zygapophyseal) joints [8]. Among the roughly 13% of the population who go on to develop chronic neck pain [13], the cervical zygapophyseal

462 Kai On SUN, Henry Ka Fai TONG

joints have been postulated to account for between 50–60% of cases based on diagnostic, controlled blocks [2, 21, 23]. Two factors which may account for the high incidence of cervical facet joint pain in chronic neck pain sufferers are the higher density of mechanoreceptors in cervical compared with lumbar facet joints [6] and their susceptibility to injury during trauma. The precise pathophysiology of facet joint syndrome is often unclear. Two medial branches of the dorsal rami provide innervation. There is no pathognomonic symptom or sign, laboratory, radiological, or electrophysiological diagnostic test. By convention, the diagnosis is based simply on a constellation of findings. Facetinduced back pain is currently a diagnosis of exclusion supported by reproduction of the pain during arthrography and abolition of pain following injection of local anaesthetic. Therefore, there is no facet syndrome per se as there is no combination of clinical features which defines facet joint syndrome. However, one recent retrospective study showed that there is strong correlation between paraspinal tenderness and radiofrequency treatment success in cervical facet pain patients [9]. The facet joints are paired diarthrodial synovial joints formed by the inferior articular process of one vertebra and the superior articular process of the subjacent vertebra. A tough fibrous capsule is present on the posterolateral aspect of the facet joint. Owing to the small volume of the lumbar facet joint space, approximately 1 to 2 ml, volumes of therapeutic agent in excess of this amount may extravasate into the epidural space by the ventral aspect of the joint. The poor localisation of facet joint pain is explained by the pattern of profuse overlapping of sensory innervation of these joints. The medial branch of the posterior ramus supplies the lower pole of the facet joint at its own level as well as the upper pole of the facet joint below. Each medial branch of the posterior primary ramus also supplies the multifidus and interspinalis muscles, as well as the ligaments and periosteum of the neural arch. Therefore, pain relief after lumbar facet nerve block cannot be regarded as specific to the facet joint. Because of the duality of segmental innervation, each joint must be denervated at two segmental levels, both at and above the level of the involved joint. The medial branches of the cervical posterior rami are somewhat different in that they mainly supply the facet joints, with only small discrete innervations of the posterior neck

muscles. Therefore, if neck pain or headache is due to cervical facet disease, it is likely to be relieved by cervical facet joint or medial branch blocks. Please also refer to Chapter 12 for more information on neck pain. In patients with lumbar facet joint disease, the history is likely to include complaints of deep, achy, nonspecific low back pain localised over the affected facet joint. Radiation to the buttock or proximal thigh is possible. Pain occasionally radiates below the knee but not into the foot. The patient may report that the symptoms are worse with lumbar extension, extensive walking, or sitting for long periods of time. There is no bowel or bladder dysfunction. On physical examination, the patient demonstrates pain with deep palpation over the affected facet joints. There may be associated paraspinal muscles spasm. The patient does not have focal or segmental muscle atrophy, neural tension signs, or true strength deficits. Facet joint changes on radiography are nonspecific as they are almost ubiquitous in adults. Some studies, however, have suggested that computed tomography (CT) may be very helpful in diagnosing significant abnormalities of facet joints. Please also refer to Chapter 13 for more information on back pain. Once all myelopathic processes have been ruled out, a 4- to 6-week course of conservative therapy is indicated. Interventional procedures can be considered if symptoms persist. Fluoroscopically guided joint space or medial branch block injections must reduce the pain by more than 50% to be considered successful. There are conflicting data regarding the efficacy of radiofrequency ablation of the nerve supply to the facet joint. The facet joint can be blocked by local anaesthetics and steroid or denervated with cryotherapy and radiofrequency lesioning. The contraindications to facet blockade are similar to those for any regional block. Facet blocks should not be performed in patients with coagulopathies, systemic infection, or infection at the site of injection.

Injection of lumbar facet joints and medial branch block The normal lumbar facet joint has an S-shaped contour in the oblique projection. The capacity of the joint is 1 to 2 ml. Facet joints can be entered from a posterior approach. The patient is placed in

Interventional Procedures for Back and Neck Pain 463

Figure 28.01

Figure 28.02

RF denervation of lumbar facet joint positionin

Figure 28.03

RF denervation of lumbar facet joints needle in

Lumbar vertebra Scottie Dog appearance

the prone position on the X-ray table with a wedge sponge placed beneath the abdomen, and with the hip and knee flexed to decrease the lumbar lordosis. The symptomatic side is rotated up while visualising the facet joint under fluoroscopy to determine the optimum obliquity. The minimum obliquity that allows visualisation of the facet joint is usually best for facet injection. Because this is often achieved at nearly 45°, the C-arm is usually rotated to this angle for better visualisation of the facet joints. The joints to be blocked should be identified and marked before initiation of the injection. When the patient is properly positioned for lumbar facet blockade, a “Scottie dog” configuration can be clearly visualised under fluoroscopy. The joint capsule is defined by the “ears” and “back” of the head of one “Scottie dog” and the vertebra above by the “dog’s” front feet (Fig. 28.01). At each joint to be blocked, the caudal edge of the spinous process corresponding to the level of the facet joint is identified. After prone positioning and under image intensifier guidance, a 22G or 25G x 35 mm spinal needle is then inserted into the joint (Figs. 28.02 and 28.03). Radiocontrast 0.25 to 0.5 ml can be injected to visualise the S-shaped joint space and confirm proper needle placement. This is followed by injection of bupivacaine and 20 mg methylprednisolone acetate (for each joint). Some practitioners advocate the use of larger volumes (2 to 5 ml) for pericapsular rather than intraarticular injection. This type of injection bathes the ligaments, paraspinal muscles and supporting

structures with local anaesthetics and steroid. This has been beneficial to some patients with chronic low back pain of multifactorial origin. In medial branch blocks, a spinal needle is introduced approximately 5 cm lateral from the midline and directed obliquely, in order to avoid the overhang of the articular process (Fig. 28.03). This involves injecting a tiny amount of local anesthetic (0.3 ml), under fluoroscopic control, onto each of the medial branches. From L1 to L4, the medial branch is blocked where it lies in a gutter on the dorsal surface of the transverse process, just caudal to the most medial end of the superior edge of the transverse process. The posterior primary ramus of L5 is blocked as it runs in the groove between the ala of the sacrum and the superior articular process of the sacrum (Fig. 28.04). The blocks require a preliminary test dose of contrast medium, because in about 8% of cases the injection can be into

464 Kai On SUN, Henry Ka Fai TONG

Injection of cervical facet joint and medial branch block For medial branch nerve blocks of C3 through C8, a 10 cm spinal needle should be inserted 1 to 2 cm lateral to the waist of the articular pillar as seen by posteroanterior view under fluoroscopy. The needle is advanced until it contacts the back of the articular pillar and then is redirected laterally until the needle tip is at the most lateral margin of the articular pillar. Intra-articular blockade of cervical facets C3 through C7 can be performed by using a 10-cm spinal needle inserted one to two levels below the joint to be blocked. The needle is then advanced upwards and forwards into the middle of the joint under the fluoroscopic guidance.

Figure 28.04

RF lesioning of lumbar facet joints

the vena comitans of the medial branch. Venous uptake is usually not a major problem, given the small volume of local anesthetic injected, but it risks obtaining a false-negative response. Lumbar medial branch block has a false-positive rate of between 25% and 41% [30]. Placebo controls provide the highest order of validity, but they are difficult to implement in clinical practice as multiple blocks would need to be performed on separate occasions to assess response to placebo and active agent. Less discriminating but more practical are comparative local anesthetic blocks. On each of two occasions, the patient receives an active agent, but the agents are varied. When a short-acting agent is used, the patient should obtain shortlasting relief. When a long-acting agent is used, the patient should obtain long-lasting relief. When tested against placebo, this protocol has a sensitivity of 54% and a specificity of 88% [20]. A transient exacerbation in pain (about 2% incidence) can be experienced lasting as long as 6 weeks to 8 months in rare cases. Spinal anaesthesia has occurred after facet joint injection.

Blockade of the innervation of the C2–C3 facet joint requires location of the third occipital nerve. The needle is inserted until it contacts the C2–C3 facet joint and then is redirected laterally until it reaches the lower half of the lateral margin of the facet. Proper positioning of the needle should be confirmed by fluoroscopy. After 1 to 2 ml of medication is injected, the patient should be assessed for suboccipital numbness, which indicates adequate blockade of the third occipital nerve and innervation of the C2–C3 facet joint. The atlanto-axial joint can be blocked using a 22G spinal needle to enter the joint posteriorly and then directing the needle onto the lateral half of the posterior capsule under fluoroscopic guidance. Confirmation with both posteroanterior and lateral X-ray views is needed to ensure that the needle is in the middle of the joint before injection of medication. The practitioner should be aware that the epidural space lies immediately medial to the joint capsule and that the vertebral artery lies just lateral to it. Use of more than a total of 2 ml of injectate may result in leakage outside the joint capsule with subsequent blockade of the cervical spinal nerve roots. This can lead to high spinal block and respiratory arrest. Bogduk and associates recommend the use of medial branch nerve blocks rather than intraarticular injections in the cervical area [5, 27]. This is because the medial branch nerve blocks are easier to perform and possibly less traumatic than intra-articular injections. Also, the medial branch nerves are fairly superficial and easily accessible,

Interventional Procedures for Back and Neck Pain 465

and the blocks can be successfully performed in patients with facet joint disease which has resulted in obliteration of the joint space. Furthermore, theoretically, there is less risk of penetration of a vertebral artery, the epidural space, or the dural sac than with intra-articular injections.

Radiofrequency lesioning facet joint Radiofrequency (RF) lesion generation has certain advantages over other techniques. Modern RF generators (Fig. 28.05) and cannulas (Fig. 28.06) allow precision thermal lesion placement, minimising damage to surrounding tissue. Various cannulas are available to produce different lesion sizes and shapes. Continuous temperature monitoring gives the operator additional control over lesion size. Impedance monitors detect electric circuit malfunctions and may signal close proximity to bone (high impedance) or blood vessels (low impedance).

Figure 28.05 Radiofrequency Machine with permission from Baylis Medical Inc.

Radiofrequency heat lesions are produced by exciting ions within a field of alternating electric current at 500,000 Hz. As current density decreases rapidly with distance from the electrode tip, the volume of the lesion is limited. The determinants of lesion size are electrode size, tissue conductivity (water content), adjacent tissues (bone, blood vessels and cerebrospinal fluid) and RF generator output. Heating tissue to 80°C for 60 seconds creates a maximal lesion. A clinical effect may also be possible, without heating the tissue significantly, using pulsed RF energy. Before RF lesioning, the operator should always ensure that the temperature meter reads body temperature at about 37°C. This is the simplest check that the temperature monitor is functioning. The patient is placed in a prone position on a fluoroscopic table (Fig. 28.02). It is important to keep the patient awake enough so that they can cooperate during the procedure. The patient’s back is prepared and draped in a sterile fashion. A C-arm fluoroscopic device is used for localisation of the RF target sites. Radiofrequency lesioning targeting the L5–S1 facet involves first positioning the RF probe at the superior and lateral aspect of the S1 foraminal opening (Fig. 28.07). A small branch exits the

Figure 28.06

RF Probes

superior lateral aspect of the S1 foraminal canal and extends in a superior fashion towards the base of the L5–S1 facet joint. At the S1 level, the fluoroscopic unit needs to be angled in a cranial fashion to correctly show the opening of the S1 foraminal canal. It is important to place the RF

466 Kai On SUN, Henry Ka Fai TONG

and alar levels are not too close to the opening of the foraminal canals.

Figure 28.07 RF lesioning of L5S1 facet joint

cannula in a parallel fashion to the X-ray beam so that it touches the periosteum at the superior lateral border of the S1 foramen. A second target zone includes the superior and medial junction of the sacral ala. (Fig. 28.07) A posteroanterior fluoroscopic view usually gives correct imaging for placement of the cannula. The cannula is advanced until it touches the superior medial border of the sacral ala and after the periosteum has been contacted, the cannula is walked over the leading edge and advanced approximately 2 to 3 mm in an anterior fashion. The other target zones include the superior and medial aspect of the transverse processes at the respectively involved L5, L4 and L3. That is, the junction of the transverse process with the superior articulating process of its respective facet joint (Fig. 28.04). An oblique fluoroscopic view between 5° and 15° is usually necessary to show the most medial aspect of the transverse process. After the cannula touches the periosteum at the superior and medial border of the transverse process, the cannula is walked over the leading edge and advanced approximately 2 to 3 mm in an anterior fashion. This is done to more correctly align the tip of the cannula with the facet joint nerve. The idea is to place the length of the cannula tip parallel to the length of the nerve in order to create a longer lesion which will hopefully produce a longer clinical result. After the cannula has been placed in the correct position, a lateral view is taken to make certain that the cannulas at the L3, L4, L5

It is important to check impedance monitoring at least one time after the cannula has been placed. The average impedance during a facet rhizotomy is between 400 to 700 ohms. Once the cannulas are in the correct position, electrical stimulation is performed at 50 Hz. Good paraesthesia to the back, paravertebral, or hip region should be noted when the medial branches at these levels are stimulated. Good stimulation should be noted at less than 1 volt at 50 Hz if the electrode system is in correct alignment with the medial branch. Next, electrical stimulation is performed at 2 Hz and lower extremity motor fasciculation should be absent at 3 volts stimulation. After showing correct dissociation between sensory and motor stimulation it can be assumed that the cannulas are in the correct position. At that point, 1 ml of 2% lignocaine is injected through each cannula and a 30-second delay is allowed to occur. Thermal lesions are then created at each level by heating the nerve for a period of 90 seconds at a temperature of 80°C. After the lesions are created, the cannulas are removed and sterile bandages are placed at the puncture sites. Sometimes patients will notice lower extremity weakness immediately following the procedure. This is due to extravasation of local anaesthetic solution onto the main nerve root. This phenomenon will resolve within 1 to 2 hours after the procedure. It can be expected that the patients will have up to 2 weeks of discomfort involving pain in the paravertebral regions and the upper buttock following the procedure.

Cryoneurolysis of the facet joint Cryoanalgesia, the relief of pain by application of cold, has been used for millennia. Only gas expansion (the Joule-Thompson effect with CO2 or N2O) cryomachines are used for pain control today. Important features of the cryomachine include a thermocouple at the tip to monitor temperature, a nerve stimulator at the tip allowing both motor and sensory stimulation for nerve localisation, a flowmeter to monitor high pressure gas flow, a pressure gauge to monitor cylinder contents, and freeze and defrost indicators. A temperature of -20°C must be reached in the tissues to result in uniform cell death. When using

Interventional Procedures for Back and Neck Pain 467

a gas expansion cryoprobe, which cools to -70°C (using N2O), the center of the ice ball must be within approximately 4 to 5 mm of the nerve for lethal application. In contradistinction to the more severe nerve injuries (induced by radiofrequency, phenol and alcohol), cryoneurolysis preserves the fibrous architecture, especially the endoneurium, allowing more organised regeneration without neuroma formation and a low incidence of neuritis. The technique involved is similar to those for RF lesioning of the facet joint. In medial branch denervation, the silver-tipped 5-inch cryoprobe can be used. The lesion needs to be frozen at -60°C to -70°C for 2 to 4 minutes. It is repeated two to three times, ensuring adequate thaw times between freezes. The ice ball should not be removed from the tissue. It is necessary to wait until it is completely thawed before pulling out the cryoprobe. Since the cryoprobes are relatively large, this may result in significant intervening tissue trauma and for this reason, radiofrequency neurolysis has largely supplanted cryoneurolysis in most pain clinics.

Sacroiliac Joint Pain The sacroiliac (SI) joint can produce symptoms that are quite similar to facet joint pain. Areas of referral include the hip, groin, anterior thigh and calf. Examination usually shows distinct tenderness over the middle and lower aspect of the SI joint. Compression tests are frequently painful and distraction tests often reveal a poorly mobile joint. Other tests such as Faber and Patrick tests are also useful. Sacroiliac joint problems frequently exist in conjunction with other musculoskeletal disorders such as myofascial pain syndrome, which must be treated to ensure complete relief. The SI joint can be a primary source of pain. Pain may be referred to the SI joint or from the SI joint to the lumbar facets, iliolumbar ligament, and gluteal, piriformis, iliopsoas and adductor muscles. Visceral pain referral may occur from the reproductive organs and from the large intestine. Systemic conditions such as ankylosing spondylitis, regional ileitis and gout can also produce pain in the SI joint. Primary SI problems are frequently the result of an accident or injury, but they also can result from an unguarded or unexpected movement, chronic strain in the workplace, or repetitive activity such

Figure 28.08

Radiofrequency lesioning of sacroiliac joint

as swinging a golf club. Sacroiliac joint pain is not uncommon during or following pregnancy. Sacroiliac joint problems can be treated by injection or manipulation. Techniques used for manipulation may involve high velocity, low amplitude thrust techniques or muscle energy techniques, which are a form of precise contract-relax stretching to mobilise the joint. With the patient lying in a prone position, the skin entry point should be 1–3 cm below the inferior margin of the SI joint. At this point, the skin is infiltrated with 1% lignocaine. Under fluoroscopic control, a 22/25G spinal needle is introduced and directed cephalad to strike the ilium 1 cm above the inferior margin of the target joint. The tip of the needle is then manipulated until it enters the joint space. One ml of contrast medium is injected. The latter initially fills a small inferior, subcapsular recess and then extends to the superior aspect of the joint. Meanwhile, the injection can produce similar pain to that which has been experienced by the patient. After the injection of contrast medium, the joint is infiltrated with 1 ml of 2% lignocaine. For RF rhizotomy under image intensifier guidance (Fig. 28.08), the fluoroscopy unit is angled in such a way that the lines of the posterior and anterior aspects of the joint are seen to overlap. The tube is angled caudad and obliquely from the side opposite

468 Kai On SUN, Henry Ka Fai TONG

a compression injury causing end-plate fracture; this in turn triggers inflammatory degradation of the nucleus pulposus and eventually of the annulus fibrosus in the form of annular fissures. The disc becomes painful as a result of chemical irritation of nerve endings in the outer annulus. The condition is sometimes not evident on CT and it does not cause neurological symptoms. The annular fissures can be demonstrated on magnetic resonance imaging (MRI) scans with the use of gadolinium. However, both CT and MRI do not tell us whether the pathoanatomy is symptomatic. Therefore, the gold standard is still the discography procedure [11]. Figure 28.09

SKJ RF denervation targets

the joint to be lesioned; that is, an oblique view at 15° to 20° from the opposite side of the body is used to correctly visualise the posterior joint lines. The favoured technique used to denervate the SI joint involves the production of multiple connecting linear lesions along the entire length of the posterior aspect of the joint and its capsule. (Fig. 28.09) Each lesion is created by increasing the temperature to 80°C for 60 seconds. It is important to make certain that the lesions overlap slightly so that a complete linear lesion is produced along the entire posterior joint line. The S2 level contributes heavily to the innervation of the SI joint. An S2 ganglionotomy can be an important adjunct to the SI joint rhizotomy. Patients usually experience 2 weeks of buttock discomfort following the SI joint rhizotomy. Patchy decreased skin sensation in the buttock is sometimes seen and uniformly resolves within 2 to 6 weeks.

Discogenic Back Pain Discogenic pain is typically a deep, dull midline aching in the low back that might radiate to the gluteal areas but is rarely experienced below the knees or legs. It can be categorised into three entities: internal disc disruption, degenerative disc disease, and segmental instability. Internal disc disruption should not be confused with disc herniation or disc degeneration. Please also refer to Chapter 12 for more information. The aetiology of internal disc disruption has not been definitively established, but it probably results from

Discography is an invasive diagnostic procedure designed to ascertain whether a disc is intrinsically painful, and is the single most important test for diagnosing internal disc disruption. It stimulates the disc by increasing the intervertebral pressure and reproducing the patient’s pain. It can be done anywhere in the cervical, thoracic, or lumbar discs, with the lumbar being the most common. Patients who are not candidates for definitive management of discogenic pain (surgery, intradiscal electrothermal therapy) are not candidates for discography. Broad spectrum antibiotic are given before the procedure [12]. The patient is placed in the prone position. Usually one disc above and one below the suspected level are also injected as control levels, and the suspected level is injected last. The following parameters are noted: resistance on entry to the annulus, compliance of the nucleus on injection, pain provocation on injection, and distribution of dye inside and outside the disc. Antibiotics and local anaesthetics are injected before withdrawing the needle at each level. The administration of both systemic and intradiscal antibiotics has been shown to be necessary by Fraser et al. who in sheep studies noted antibiotic levels in the annulus 30 minutes after intravenous administration, but none was demonstrated at 60 minutes [12]. Furthermore, once the discitis is developed, it is very difficult to treat. Anteroposterior and lateral discographic images are then obtained as well as a post-procedure CT scan within 2 hours to highlight the features of the internal disc disruption. Replication of usual pain at less than 50 psi above opening pressure is considered positive for the test and can either proceed to surgery (interbody fusion) or intradiscal electrothermal annuloplasty/nucleoplasty,

Interventional Procedures for Back and Neck Pain 469

radiofrequency lesioning and laser-assisted spinal endoscopy.

Intradiscal electrothermal procedure

extremity motor stimulation. One ml of 2% lignocaine is then passed through the RF cannula and a 60-second delay is allowed for it to take effect. A thermal lesion is created by heating the lesion for a period of 60 seconds at 80°C.

The intradiscal electrothermal (IDET) procedure utilises an intradiscal catheter designed to achieve precise navigation and placement in the disc. The catheter delivers intradiscal thermal energy. The mechanism of analgesia is not entirely clear, although there is evidence that the collagen fibres in the annulus undergo structural changes, so annular fissures can heal thereby reducing pain. It is not recommended that more than two levels at one time be treated. Signs of improvement usually occur 6 to 12 weeks after the procedure. Exclusion criteria for IDET are: intervertebral disc herniation with radiculopathy, disc height decreased for more than 50%, spinal stenosis, prior discectomy and coagulopathy.

For the RF lumbar disc procedure, the patient is again put into a prone position and preoperative antibiotic is given to prevent postoperative disc infection. The fluoroscopic unit is angled at 15° to 20° from an oblique approach to correctly image the painful disc. The RF cannula is advanced in a percutaneous manner until it contacts the disc annulus. The cannula is passed into the disc and advanced until it enters the central aspect of the nucleus as seen by posteroanterior and lateral views. Electrical stimulation is checked at 2 Hz for motor stimulation. If a 10 mm active tip is used, then a 4-minute 80°C lesion is created; if a 15 mm active tip is used, a 4-minute 70°C lesion is performed. No intradiscal local anaesthetic is used.

Radiofrequency procedures for discogenic pain

It is not unusual to develop mild dysaesthesias that last for 7 to 10 days following RF lesioning of the ramus communicans nerve or intradiscal procedure. These are related to low-level heat injury of the lumbar nerves. The vast majority of such dysaesthesias resolve without complication within 3 weeks.

Radiofrequency techniques developed for the treatment of lumbar discogenic pain include radiofrequency lesions of the ramus communicans nerves as well as intradiscal RF lesions. The ramus communicans nerve sends fibres to more than one level and if discography has shown that the L4–L5 disc is the painful level, then lesions of the ramus communicans nerves should be performed at L4 and L5. The patient is placed in the prone position and RF cannulas measuring 150 mm in length with 5 mm active tips are selected. The end plates of the disc and the vertebral body should be clearly visualised by fluoroscopy. Oblique angulation at 15° to 25° is used so that the body of the vertebra just covers the lateral tip of the transverse process. The ramus communicans nerve tends to run at the lower third of the vertebral body. The RF cannula is advanced until the periosteum at the lower third of the vertebral body is contacted. The cannula is advanced until halfway between the anterior and posterior borders of the vertebral body in the lateral fluoroscopic view. Direct contact with the periosteum should be maintained at all times. Electrical stimulation is then performed, which produces a deep aching sensation in the back with 50 Hz stimulation at 1.0 volt. Stimulation with 2 Hz at 2.5 volts should fail to produce lower

Epiduroscopy and Epidurolysis Lumbosacral radiculopathy is suggested by complaints of pain, sensory disturbance, weakness, or reflex asymmetry in the distribution of a distinct lumbosacral nerve root. Most lumbosacral radiculopathies involve the L5 or S1 root and most causes can be managed with conservative care. Herniated intervertebral disc, spinal stenosis, spondylolisthesis, infection and neoplasm can all cause lumbosacral radiculopathy. Sinister causes should be ruled out before treating the patient conservatively. Epidural endoscopy has been used in the diagnosis and treatment of patients with chronic radicular pain without evidence of disc injury. Visualisation of inflammatory changes in the nerve roots corresponding to the patient’s symptoms can be useful in establishing mechanical compression as

470 Kai On SUN, Henry Ka Fai TONG

the basis for the patient’s complaints. The work of Racz and associates suggested that lysis of epidural adhesions was of significant benefit to many patients with refractory lumbar radiculopathy [28]. The adhesion formed in the epidural space of patients with chronic spinal pain syndrome after surgery or perhaps as a result of inflammation, may be responsible for pulling and tugging nerve roots and the dural sac. Epidural endoscopy is usually performed with the patient in the prone position using the caudal approach via the sacral hiatus. A guide-wire placed through an epidural needle facilitates the insertion of a flexible and manoeuverable sheath containing separate channels for the endoscope itself and for irrigation and injection of solutions. During endoscopy, the epidural space can be visualised only if it is distended by repeated injections of saline flushing solutions. Rigorous control of the total volume of irrigation solutions is essential to prevent complications due to over-distension of the lumbar epidural space, with resultant excessive increase in intraspinal pressures. The volume limit advocated by most clinicians is 100 ml. Cases of macular haemorrhage and visual impairment following the procedure have been reported. Epidural endoscopy allows mechanical lysis of the adhesion that entraps the corresponding symptomatic root by applying gentle manipulation of the fibrescope and injection of different medications at the site of the pathological findings. Injections of corticosteroids, hyaluronidase, clonidine, hypertonic saline and opiates have been described in the literature. The reason for using this injection technique is the failure of the usual method of epidural steroid injection to deliver the drug to the pathological areas because of fibrous scar tissue or adhesions. Epidural endoscopy offers a sensible approach to treat a group of patients in which other treatment options are more invasive and require either a repeat surgical procedure or the use of implantable devices for pain control. Spinal cord stimulation will be discussed in Chapter 30.

Vertebroplasty and Kyphoplasty Osteoporotic compression fracture is a common condition in the elderly. It is estimated that more

than one-quarter of women aged over 65 years will develop a vertebral fracture due to osteoporosis. Percutaneous vertebroplasty is a relatively new procedure which involves injecting polymethylmethacrylate cement into the osteoportic vertebral body fracture percutaneously. By stabilising vertebral lesions, the injected cement produces analgesia in these patients. It is an outpatient procedure, performed under fluoroscopic or CT guidance. Prophylactic antibiotics are administered to the patient approximately 30 minutes before the procedure. The patient is placed in the prone position and after local anaesthesia, an 11G bone marrow biopsy needle is directed using a transpedicular approach into the vertebral body. Both lateral and anteroposterior projections provide necessary visualisation of the path of the needle. After confirming needle placement in the lateral fluoroscopic views and negative intravascular contrast spread, the cement is injected under continuous fluoroscopic guidance into the collapsed segment. The alternative parapedicular approach involves inserting the cannula between the lateral margin of the pedicle of the thoracic vertebrae and the ribs’ head [15]. Anteroposterior images are checked regularly to monitor for lateral leaks. Typically, the injection must be completed in 6 to 8 minutes before the cement becomes too viscous to allow reinsertion of the stylus. The cement will set within 20 minutes and achieve 90% of its strength within an hour [25]. Pain relief is expected to be noticed in 4 to 24 hours. Potential complications include leakage of cement into adjacent structures, with neural damage due to mechanical compression, theoretical risk of systemic embolism and thermal necrosis. This procedure has caused fear that cement extravasation could have devastating neurological consequences from intrusion and that the high pressures used to introduce the cement could potentially lead to the bolus embolisation of cement through the venous channels in the vertebral body to the lungs. Additionally, vertebroplasty was felt to be an inadequate means of fracture reduction. As the result of these concerns, the kyphoplasty technique was devised and was first performed in 1998. Kyphoplasty is a safer procedure because it involves the injection of cement with lower pressure. Patients who undergo this procedure usually receive general anaesthesia because elderly patients do not tolerate the prolonged prone position required. The procedure can be performed via the

Interventional Procedures for Back and Neck Pain 471

transpedicular or peripedicular approach. A 1-cm incision is made just lateral to both pedicles of the vertebral body to be treated. A Jamshidi needle is used to enter the superior lateral border of the pedicle under fluoroscopic guidance. Frequent anteroposterior and lateral fluoroscopic images are used to confirm position. Once the Jamshidi needle enters the vertebral body, the needle is exchanged for an obturator followed by a working cannula. A drill is then used to create a tract into the vertebral body. The balloon catheter is introduced into the fracture site and the process is repeated on the contralateral side. Both balloon tamps are then inflated until either the fracture is reduced or it is felt unsafe to continue. The balloons are then removed and the cavities are filled with methylmethacrylate cement using a hand plunger system. Intraoperative radiographs are used to confirm containment of the cement in the vertebral body [19]. It is important to note that The US Food and Drug Administration warns that a type of bone cement used to treat spinal fractures may cause serious side effects, reports United Press International. (FDA

Issues Bone Cement Warning — November 7, 2002). According to the FDA alert, two procedures, vertebroplasty and kyphoplasty, have been linked to tissue damage and nerve root pain due to the bone cement, called poly-methylmethacrylate, leaking into the body. Without releasing numbers, the agency also said it had received reports of blood clots in the lungs, respiratory and cardiac failure, and even death.

Conclusion Chronic neck and low back pain can have a significant impact on the daily activities of patients. Symptoms may also result from more than one pathology; for example, disc degeneration can lead to facet joint syndrome due to altered biomechanics. Importantly, psychosocial issues may further perpetuate the pain, even if the interventional pain treatment seems to be successful. Therefore, a holistic, multidisciplinary multimodal approach is required in treating patients with chronic neck and back pain, as these patients often have work-related injuries.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Aronoff GM, Evans WO, Enders PL. A review of follow-up studies of multidisciplinary pain units. Pain 1983;16:1– 11. Barnsley L, Lord SM, Wallis BJ, et al. The prevalence of chronic cervical zygapophyseal joint pain after whiplash. Spine 1995;20:20–6. Benzon HT. Epidural steroids. In:Raj PP, ed. Pain Medicine: A Comprehensive Review. St. Louis: Mosby, 1996. Berstein RM. Injection and surgical therapy in chronic pain. Clin J Pain 2001 Dec;17(4 Suppl):S94-104. 3. Bogduk N. Lumbar facet syndrome. In Waldman SD eds Pain Management Volume 2, Elsevier 2007:Ch84. Bogduk N. Back pain: Zygapophysial blocks and epidural steroids. In Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anaesthesia and Management of Pain, 2nd edn. Philadelphia: JB Lippincott, 1988:935–46. Bogduk N. Clinical Anatomy of the Lumbar Spine, 3rd edn. New York: Churchill Livingstone,1997:33–41. Borghouts JA, Koes BW, Vondeling H, et al. Cost-of-illness of neck pain in the Netherlands in 1996. Pain 1999;80:629– 36. Cavanaugh JM, Ozaktay AC, Yamashita T, et al: Mechanisms of low back pain: A neurophysiologic and neuroanatomic study. Clin Orthop 1997;335:166–80. Cohen SP, Bajwa ZH, Kraemer JJ, et al. Factors predicting success and failure for cervical facet radiofrequency denervation: A multi-center analysis. Reg Anesth Pain Med 2007;32(6):495–503. Derby R, Bogduk N, Kine G. Precision percutaneous blocking procedures for localizing spinal pain. Part 2: The lumbar neuroaxial compartment. Pain Digest 1993;3:175–88. Derby R, Howard MW, Grant JN, et al. The ability of pressure controlled discography to predict surgical and nonsurgical outcomes. Spine 1999;24:364. Fraser RD, Osti OL, Vernon-Roberts B. Iatrogenic discitis: The role of intravenous antibiotics in prevention and treatment. An experimental study. Spine 1989;14:1025.

472 Kai On SUN, Henry Ka Fai TONG

13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30.

Guez M, Hildingsson C, Stegmayr B, et al. Chronic neck pain of traumatic and non-traumatic origin: A populationbased study. Acta Orthop Scand 2003;74:576–9. Hasue M, Kikuchi S, Sakuyama Y, et al. Anatomic study of the interrelation between lumbosacral nerve roots and their surrounding tissue. Spine 1983;8:50–8. Hide IG, Gangi A. Percutaneous vertebroplasty: History, technique and current perspectives. Clin Radiol 2004;59:461– 7. Kikuchi S, Hasue M, Nishiyama K. Anatomic and clinical studies of radicular symptoms. Spine 1984;9:23–30. Kikuchi S, Sato K, Konno S, et al. Anatomic and radiographic study of dorsal root ganglia. Spine 1994;19:6–11. Kurobane Y, Takahashi T, Tajima T, et al. Extraforaminal disc herniation. Spine 1984;11:260–8. Lavelle WF, Cheney R. Recurrent fracture after vertebral kyphoplasty. Spine J 2006;6(5):488–93. Lord SM, Barnsley L, Bogduk N. The utility of comparative local anaesthetic blocks versus placebo-controlled blocks or the diagnosis of cervical zygapophyseal joint pain. Clin J Pain 1995;11:208. Lord SM, Barnsley L, Wallis BJ, et al. Chronic zygapophyseal joint pain after whiplash: A placebo-controlled prevalence study. Spine 1996;21:1737–44. Manchikanti L. Role of neuraxial steroids in interventional pain management. Pain Physician 2002;5:182. Manchikanti L, Singh V, Rivera J, et al. Prevalence of cervical facet joint pain in chronic neck pain. Pain Physician 2002;5:243–9. Maniadakis N, Gray A. The economic burden of back pain in the UK. Pain 2000;84:95–103. Mathis JM, Barr JD, Belkoff SM, et al. Percutaneous vertebroplasty: A developing standard of care for vertebral compression fractures. Am J Neuroradiol 2001;22(2):373–81. Ng KFJ, Tsui SL, Chan WS. Prevalence of common chronic pain in Hong Kong adults. Clin J Pain 2002;18:275– 81. Pawl RP. Headache, cervical spondylosis, and anterior cervical fusion. Surg Ann 1971;9:391. Racz GB, Holubec JT. Lysis of adhesions in the epidural space. Techniques of Neurolysis. Boston: Kluwer Academic, 1989. Ramamurthy S, Alanmanou E, Rogers JN. Decision Making in Pain Management, 2nd edn. San Antonio, Mosby Elsevier,2006:302–3. Schwarzer AC, Aprill CN, Derby R, et al. The false-positive rate of uncontrolled diagnostic blocks of the lumbar zygapophyseal joints. Pain 1994;58:195.

29

Kok Eng KHOR

Neuraxial Analgesia

Introduction

INTRODUCTION DEFINITION RATIONALE FOR NEURAXIAL ANALGESIA IN CHRONIC PAIN PATIENT SELECTION MEDICATIONS DELIVERY SYSTEMS FOR NEURAXIAL ANALGESIA EFFICACY COST EFFECTIVENESS RISKS AND COMPLICATIONS SPECIAL SITUATIONS

The discovery of opioid receptors and potent opioid peptides in the nervous system in the early 1970s provided the rationale for the neuraxial delivery of opioid drugs for analgesia [49, 69]. This was demonstrated in experimental animals and patients with chronic pain via intrathecal and epidural routes [11, 99, 103]. The phrase “selective spinal analgesia” was used to describe this specific analgesic state produced by a small dose of morphine without significant sensorimotor or haemodynamic side effects [21]. This heralded a new phase in the management of pain which has expanded to the area of acute postoperative, obstetrical, cancer and chronic nonmalignant pain. The first catheter for intraspinal delivery was developed by Du Pen. Later bolus injections of morphine were administered via intrathecally placed catheters which were connected to subcutaneous reservoirs. The concept of a totally implantable drug pump was developed in 1969 at the University of Pennsylvania with the first intrathecal pump to administer morphine implanted in 1981 for the treatment of chronic intractable pain [17, 97]. Neuraxial analgesia using a combination of analgesics, chiefly morphine, clonidine and bupivacaine, is fairly well established in the management of chronic cancer and non-malignant pain states. Other alternative neuraxial agents are also being introduced and tested. The delivery systems, especially those of the intraspinal catheter and the implantable pumps, are now very robust, reliable and safe, and this contributes to the efficiency of neuraxial analgesic therapy.

PATIENT MANAGEMENT CONCLUSION

Definition

REFERENCES

Neuraxial analgesia is defined as the epidural or intrathecal administration of analgesics; these are usually opioids, but

474 Kok Eng KHOR

also include those from other classes such as alpha-2 agonists, local anaesthetics and gamma aminobutyric acid (GABA) agonists for the management of severe pain.

corrective spinal decompressive and stabilisation procedures [25, 53, 55]. The place of neuraxial analgesia can be ranked in a pain treatment continuum in the multidisciplinary management of chronic pain (see Fig. 29.01).

Rationale for Neuraxial Analgesia in Chronic Pain

Scrupulous patient selection through a multidisciplinary assessment is mandatory for a successful clinical outcome. Patients should have a clear medical diagnosis which would account for the presenting signs and symptoms and be supported by documented evidence of nociceptive source and/or neuropathy from investigations [62]. Patients with nociceptive or neuropathic pain may be suitable candidates for neuraxial analgesia, although the latter may require higher opioid doses and addition of adjuvants [48, 70]. For cancer pain, neuraxial analgesic administration may be considered when patients are unable to control their pain with conventional management using the World Health Organization (WHO) opioid/ adjuvant analgesic ladder or in those intolerant to high-dose opioids due to systemic side effects [53, 72].

The spinal cord is the major relay pathway for nociceptive processing and modulation involving multiple neurotransmitters, receptors and intracellular mediators. By delivering the opioid analgesics, such as morphine, directly to the site of action, equivalent or better analgesia can be achieved with a small fraction of the systemic dose and a lower incidence of central nervous system (CNS) and systemic side effects such as sedation [74, 96]. Other “selective” agents such as clonidine and subanaesthetic doses of bupivacaine can be used to target other mechanisms of nociceptive processing in the spinal cord. Their co-administration enhances the analgesic effect of the opioid by an additive or synergistic action. They allow an overall reduction in dosages of the neuraxial opioid and prevent their escalation and thereby further reduce the risk of side effects and development of tolerance. In addition, incident pain and neuropathic pain syndromes which are inadequately controlled by conventional treatments and single-drug therapy may be more responsive to the drug combinations [25, 53, 65, 79, 96].

Patient Selection Indications for neuraxial analgesia Neuraxial analgesic therapy is a costly and invasive intervention with associated risks and complications. It is considered, therefore, only when less invasive pain treatments have been exhausted, such as when severe pain continues to be experienced, compromising the patient’s quality of life, or side effects from systemic analgesics become intolerable. Benefits of neuraxial therapy must clearly outweigh the risks. It should also be considered as the-end-ofthe-line therapy after spinal cord stimulation and

Suitable patients for neuraxial analgesia are those with at least a partially opioid responsive pain and those with widely distributed areas of pain who may not be suitable for nerve blocks. Nociceptive and neuropathic pain syndromes which may be amenable to neuraxial analgesic therapy are listed in Table 29.01.

Psychological assessment [54, 55, 65, 73] Unlike cancer pain with ongoing tissue destruction, chronic non-malignant pain often occurs with no tissue damage and psychological factors play an important role in the pain presentation. When considering implantable therapies, even before the screening trial, a thorough psychological evaluation with a clinical psychologist (or psychiatrist) is essential. This is to rule out serious psychopathology or a psychological aetiology for the pain and to delineate the psychological issues associated with chronic pain which may be an impediment to a successful outcome. Should remedial behavioural issues be identified, the patient should be willing to undergo mental health treatment. Major contraindications to implantation include:

Neuraxial Analgesia 475

PAIN RELIEF

Neuroablation

Increas

ing com

plexity of pain

Neuraxial analgesia

Spinal cord stimulation

Strong opioid medication

Cognitive behavioural therapies

Injection and nerve block therapies

Adjuvant analgesics

Physical therapies

Exercise and simple analgesics

PAIN

Figure 29.01 Pain treatment continuum in multidisciplinary pain management. The treatments are listed in general order of increasing complexities of pain and often used in parallel and in combination (rather than individually and sequentially)

•

• • • • •

Medical comorbidities such as coagulopathy, infection, known allergies to pump or catheter components and in the case of cancer pain, tumour encroachment of the thecal sac and patient emaciation. Major affective disorders such as depression and anxiety. Psychopathologies such as psychosis, malingering or personality disorders. Significant drug addiction issues. Excessive pain behaviours, disability and somatisation which are inconsistent with known pathology. Lack of resources for long-term management such as lack of social support and access to medical care.

Outcomes may be improved by ensuring realistic expectation, having an understanding of the

Table 29.01

Pain syndromes which may respond to neuraxial analgesia

Neuropathic pain

Complex regional pain syndromes Arachnoiditis Peripheral neuropathies Phantom limb pain Postherpetic neuralgia Spinal cord injury Plexopathy Multiple sclerosis

Mixed neuropathicnociceptive pain

Failed back surgery syndrome Diffuse cancer pain

Nociceptive pain

Osteoporosis Visceral pain Cervical, thoracic, lumbar spinal pain

476 Kok Eng KHOR

implantable device (its use and mechanism of action), the surgical procedure and follow-up, and devising strategies for coping with postimplantation pain for both the patient and patient’s support person.

Screening trial procedures After psychological clearance, adequate education and preparation, the patient undergoes a screening trial procedure. It should be conducted in a medically supervised environment where the patient can be assessed and monitored. Patients should understand the goals of the trial and that the aims are to assess the analgesic efficacy, change in functional status, behavioural response and adverse effects to the neuraxial drugs. Analgesic efficacy is determined by pain intensity, percentage pain relief and rescue analgesic used, while functional outcomes are determined by the effects on sleep, mood and activity levels [53, 71]. A variety of screening protocols exist: trials can be conducted via epidural or intrathecal administration using a bolus, a series of injections or continuous infusion; and be conducted on an inpatient or outpatient basis. The choice of protocol is influenced by the patient’s condition, physician preference, available facilities and resources [71]. There is little evidence to demonstrate the superiority of one method over another [6]. Logically, the more closely a screening trial resembles the actual conditions of the implantable pump therapy, the more accurate will the results be in mimicking those of long-term therapy. Thus, performing a trial with a continuous intrathecal infusion would be the most suitable way of assessing long-term intrathecal efficacy. A temporary lumbar percutaneous intraspinal catheter is usually placed and connected to an external pump. The daily neuraxial morphine dose infused is based on the patient’s systemic morphine dose using a morphine bioequivalent conversion of 100:10:1 for oral, epidural and intrathecal routes respectively. The patient’s usual opioid dose is reduced by 25–50%. The neuraxial dose can be increased stepwise by 50% until a positive response is obtained. Adjuvants such as clonidine can also be added to the morphine. The trial is usually conducted over a period of 3 to 5 days. To reduce the risk of a placebo response, a saline infusion can be considered. This is an important issue as up to 40% of patients who initially respond to neuraxial

analgesics fail subsequent long-term therapy [48]. Other trial variants have also been described [4, 6]. A 50% pain relief accompanied by objective evidence of functional improvements, reduced analgesic use, absence of severe adverse effects and absence of behavioural difficulties would be considered a positive response [25, 53]. A case can then be made for implantation of the intraspinal catheter and infusion pump. Additionally, especially in cancer pain, the analgesic medication needed for pain control should also be able to be replicated through the pump. If a very large volume is required, e.g. to deliver high doses of bupivacaine, this may not be feasible with the implantable pump and alternative strategies such as delivery through an externalised catheter using an external pump should be considered. For patients undergoing the placement of a tunnelled catheter-external pump system, the screening trial and catheter “implant” procedure are virtually identical [25].

Medications Opioids [12, 47, 53, 96, 97] Neuraxial opioids work by binding to pre- and postsynaptic opioid receptors in the dorsal horn and lead to the inhibition of nociceptive transmission in C fibers [97]. The main differences in the opioids relate to their lipid solubility and opioid receptor affinity, which determine their onset of action, distribution and duration of action. The quality of analgesia seems to be similar for all intrathecal opioids, although comparative data are lacking [53].

Morphine Opioids with low lipid solubility (highly hydrophilic) such as morphine diffuse slowly into the spinal cord and are bound for prolonged periods, thus accounting for the slow onset but prolonged duration of analgesia. Morphine’s hydrophilicity allows more drug to circulate throughout the cerebrospinal fluid (CSF) and ascend to the supraspinal centres. This is advantageous in terms of treating more widespread patterns of pain. Analgesia in the thoracic and cervical areas can be achieved from a lumbar-placed catheter. However, morphine’s hydrophilicity may be associated with

Neuraxial Analgesia 477

greater risk of delayed CNS side effects such as sedation and respiratory depression. Morphine continues to be the gold standard neuraxial agent because of its proven effectiveness, safety, long history and ease of use [53, 71]. Long-term stability and compatibility studies with bupivacaine and clonidine in implantable systems have also been conducted [19].

Hydromorphone Hydromorphone is about five times more potent than morphine. It is mainly used when there is intolerance or a poor response to morphine. Hydromorphone is well tolerated and has an equivalent safety, stability, compatibility with other agents and side-effect profile to morphine [7, 8, 29, 78]. Sufentanil and fentanyl These highly lipid-soluble opioids diffuse into the spinal cord rapidly but are also quickly eliminated from the CSF, thus accounting for their rapid onset but short duration of action. They spread beyond no more than a few neurotomes and placing the catheter tip in close proximity to the spinal segments involved in the nociceptive process is essential. Sufentanil is about 1000 times more lipid soluble, and has a greater potency and opioid receptor affinity than morphine. Theoretically, it would be useful in situations of morphine tolerance. A bioequivalence of 1 mg morphine to 1 mcg sufentanil is suggested for long-term intrathecal infusion [53]. A report of six patients with neuropathic pain successfully treated with long-term intrathecal sufentanil infusion showed a dose range of 12–72 mcg/day [50]. Long-term use of intrathecal fentanyl is limited to a few case reports showing an efficacious dose range of 10–115 mcg/day [95]. There is a lack of long-term neurotoxicity, stability and drug compatibility data for both these drugs [95]. Sufentanil has some weak local anaesthetic effects and may cause some hypotension and respiratory depression [53].

Methadone Methadone shows incomplete cross-tolerance to other opioids and can provide analgesia for neuropathic pain. The racemic mixture has the dual actions of a potent μ-receptor agonist and a non-competitive N-methyl-D-aspartate (NMDA)

receptor antagonist which blocks morphine tolerance and exerts neuropathic antinociception [12, 60]. A prospective case series of intrathecal methadone in patients unresponsive to other neuraxial agents reported that 54% had improved analgesia, with 38% maintaining good pain relief at 6 months at a dose range of 5–36 mg. There was significant reduction in sedation, probably because of the short half-life of intrathecal methadone. The suggested bioequivalence is about 1 mg morphine to 1.5 mg methadone [60].

Pethidine Pethidine is intermediate in its lipid solubility. Its main advantage relates to its combined opioid and local anaesthetic properties. Its higher lipid solubility limits cephalad spread and thus central side effects. There is a lack of neurotoxicity, stability and clinical data for long-term use of pethidine [12].

Non-opioid analgesics [12, 47, 53, 96, 97] Alpha-2 agonists This group of drugs binds to pre- and postsynaptic alpha-2 receptors in the dorsal horn of the spinal cord leading to the inhibition of neurotransmitter (e.g. substance P) release and C fibre transmission [97]. The prototype alpha-2 agonist is clonidine. It is used in the treatment of neuropathic pain including complex regional pain syndrome (CRPS), management of pain-related spasticity, as an adjuvant to reduce opioid tolerance and to enhance analgesia when combined with opioid [31, 79, 91, 97]. The starting intrathecal dose is about 25mcg/day, titrating gradually to about 50–300 mcg daily. The use of intrathecal clonidine monotherapy (144–1200 mg/day) in the treatment of chronic non-malignant pain was reported in a study to be successful in 42% of a cohort of patients who were resistant to opioids [44]. Smaller-dose monotherapy (10–90 mcg/day) is also effective in neuropathic pain and can be enhanced by the addition of small doses of opioids [91]. However, clonidine monotherapy analgesia can be short lived and is not always successful long term; it usually requires the addition of opioids [2]. Extensive neurotoxicity studies have found clonidine to be safe [44, 102]. Clonidine also

478 Kok Eng KHOR

maintained long-term stability in implantable infusion pumps and is compatible with morphine, hydromorphone and bupivacaine [19, 78].

Local anaesthetics Local anaesthetics bind to nerve cells and block the fast sodium channels thus inhibiting the sodium influx that initiates the action potential. They also block potassium and calcium channels. They have a predilection for unmyelinated axons and are effective even at subanaesthetic doses [97]. The main local anaesthetic which is commonly used is bupivacaine. It is rarely used as sole therapy and is often combined with morphine where it acts synergistically to enhance analgesia. Bupivacaine has been shown to re-establish analgesia when combined with morphine in opioid tolerant chronic pain states with intrathecal administration being more effective than epidural [24, 93, 97]. The starting dose is about 3 mg/day, titrating to about 4–8 mg/day; most pain relief can be achieved without significant adverse effects with intrathecal doses of less than 30 mg daily. Higher doses may not necessarily be more effective [52, 80, 82, 92]. Neurotoxicity studies of neuraxial bupivacaine at clinical concentrations in humans and animals have shown no toxicity [12, 24, 81]. However, because of the potential for neurotoxicity, it has been recommended to avoid concentrations greater than 0.75% in patients with non-cancer pain [71]. Stability testing of the drug, either as a sole agent or in combination with morphine and clonidine, showed stability and compatibility up to 90 days [19, 47]. Ropivacaine has also been used and when compared with bupivacaine showed similar efficacy and side effects; however, the required dosage range to achieve the same effect was 23% higher than bupivacaine. There are no data on safety and efficacy of longterm intrathecal use of ropivacaine [12, 47].

Ziconotide Ziconotide is the synthetic equivalent of a
conopeptide, which is present in the venom of the marine snail Conus magus. It binds selectively to N-type voltage-sensitive calcium channels on the primary nociceptive afferent nerves in the dorsal horn and blocks the release of substance P. It is administered only intrathecally. Long-

term, open-label studies showed maintenance of pain relief in about 40% of patients with a stable dose of 14 mcg/day without the development of tolerance [56]. Three randomised controlled trials confirmed ziconotide to be effective in the management of chronic intractable cancer, AIDS and non-malignant pain of diverse aetiologies with significant reduction in pain intensities and a higher proportion of patients achieving moderate to complete pain relief compared with placebo [76, 87, 98]. Ziconotide has a narrow therapeutic index and adverse events are common and can be severe. Most adverse effects are neurological and include dizziness, confusion, somnolence, memory impairment, hallucinations, vertigo, nystagmus, ataxia, gait disorders, nausea and diarrhoea. These events occur largely in the first week and resolve upon drug discontinuation. Tolerance develops slowly over time [56]. The recommended initial dosage of ziconotide is 2.4 mcg/day and dosage is titrated by ≤2.4 mcg/day at intervals of at least ≥48 hours to analgesic response or occurrence of adverse events to a maximum dosage of 21.6 mcg/day [56]. A significantly lower starting dose of not more than 0.5 mcg/day using slower titration has been recommended to significantly limit the incidence, severity and duration of side effects [34].

Baclofen Baclofenbinds to GABAB receptors in the substantia gelatinosa, opens the potassium channels and restricts calcium influx into presynaptic nerve terminals leading to hyperpolarisation and reduction of presynaptic neurotransmitters (glutamate and substance P) release [84]. It is usually used in the treatment of intractable spasticity associated with spinal cord injury. Apart from relieving pain related to spasms and spasticity, baclofen has also been reported to provide analgesia in central pain and CRPS [40, 94, 106]. It can also relieve dystonia associated with CRPS and improve function [94]. Combination therapy with clonidine and morphine has also been reported [40, 106]. The dose for antinociceptive effect is in the range of 100–250 mcg/day. Adverse effects include drowsiness, headache, confusion, hypotension, slurred speech, weight gain, constipation, nausea and sexual dysfunction. Abrupt discontinuation can lead to a potentially life-threatening withdrawal syndrome with altered

Neuraxial Analgesia 479

mental status and profound muscular rigidity. Overdosing can also be potentially life-threatening and this usually occurs during the improper refilling of the pump, such as overfilling and accidental injection into the pump pocket, resulting in loss of consciousness, seizures and cardiorespiratory depression [84]. Safety studies showed no neurotoxicity and chemical stability studies have shown sufficient stability for long-term intrathecal infusion of at least 10 weeks [47].

Midazolam Midazolam binds to GABAA receptors in the dorsal horn to produce antinociception. At the spinal level, it interacts with opioids in an additive or synergistic manner. Neuraxial administration of midazolam in chronic non-malignant pain states is still not established as neurotoxicity studies in animals remain inconclusive. There is also a paucity of safety data for long-term human administration and its use should not be routine [12, 47]. A number of case reports for severe cancer pain reported improvements when intrathecal midazolam is added to an opioid and local anaesthetic combination [3, 9].

Ketamine Although well known as an NMDA antagonist, neuraxial ketamine has limited efficacy as a sole analgesic. When used in combination, ketamine enhances the analgesic effect of morphine and reduces opioid requirement and tolerance [96, 104]. Significant psychotomimetic effects can occur with neuraxial ketamine. Neurotoxicity studies have shown histological changes and spinal cord inflammation with intrathecal ketamine which may be related to preservatives [47]. Other neuraxial agents Other neuraxial analgesics being evaluated include ketorolac, gabapentin, neostigmine, adenosine and octreotide. There is still a paucity of efficacy and safety data regarding long-term neuraxial administration of these agents and their use cannot be recommended at this time [12, 47, 96].

Drug admixture Drug combinations are used when neuraxial analgesia is compromised by development of tolerance, dose-limiting side effects and reduced efficacy of single agents. Combining drugs of different classes targets the different pathophysiological mechanisms of the pain

Use of intraspinal drug infusion in pain management — clinical guidelines

Morphine

Line 1

Hydromorphone

OR

Figure 29.02

Line 2

Morphine (or Hydromorphone) + Clonidine Morphine (or Hydromorphone) + Bupivacaine

Line 3

Morphine (or Hydromorphone) + Clonidine + Bupivacaine

Line 4

Fentanyl, Sufentanil (in place of Morphine/Hydromorphone), Midazolam, Baclofen, Ziconotide (?)

Line 5

Methadone, Ketamine, Neostigmine, Ketorolac, Octreotide, Adenosine, Ropivacaine, Pethidine

Clinical guidelines for the use of neuraxial analgesic infusion for persistent pain (adapted from Hassenbusch SJ [47], with permission from Elsevier)

480 Kok Eng KHOR

syndrome and produces additive and synergistic effects. This in turn improves analgesia and reduces the dose requirement thus also reducing drug-induced side effects [65, 79]. A smaller dose of morphine also induces less tolerance than larger morphine doses [96]. In addition, treatment of neuropathic pain, which is generally less opioid responsive, is improved by the addition of adjuvants such as bupivacaine and clonidine [25, 53, 96]. Several approaches have been proven effective.

Morphine plus clonidine Clonidine produces at least an additive and in some cases a synergistic antinociceptive effect when co-administered with neuraxial opioids leading to a reduction of the dose of opioid needed and prolongation of the duration of analgesia [96, 97]. This combination has been shown to be effective for patients with intractable neuropathic or mixed nociceptive-neuropathic cancer pain where the addition of clonidine to the epidural morphine infusion resulted in successful analgesia in 45% of patients compared to 21% receiving placebo. For those with neuropathic pain, the effect is even greater: some 56% of patients receiving clonidine reported successful analgesia as compared with only 5% receiving placebo (31).

of neuraxial analgesic agents in the management of persistent pain based on the recently held Polyanalgesic Consensus Conference in intraspinal therapy is presented in Fig. 29.02 [47].

Delivery Systems for Neuraxial Analgesia Many factors are considered in the decision to place either an external or an implantable pump system. These include the patient’s pain (type and severity), life expectancy, neuraxial dose, rates and volumes required as well as risks and costs associated with each system. As a general guide, the percutaneous externalised catheter and the tunnelled catheter with an injection port are designed for short-term use (Fig. 29.03). Both are connected to external pumps, which can be mechanical devices such as constant pressure fixed-rate spring-loaded devices and disposable fixed-rate balloon-type constant infusion devices or the more expensive electronic

Morphine plus bupivacaine The co-administration of neuraxial opioid and local anaesthetics has been shown to produce synergistic antinociception with no effect on morphine tolerance [96, 97]. In a clinical study of morphine-resistant cancer pain, analgesia improved significantly in 59% and moderately in 24% when bupivacaine was co-administered with morphine in the intrathecal infusion. There was also less rapid opioid dose escalation [93]. For cancer patients on neuraxial infusion who experience severe breakthrough pain unresponsive to systemic morphine, a breakthrough dose of intrathecal bupivacaine has been used successfully [58]. Polyanalgesic approach A polyanalgesic approach using morphine, bupivacaine and clonidine has also been advocated and shown to produce better analgesic efficacy in long-term neuraxial administration for chronic cancer and non-malignant pain than monotherapy alone [47, 74, 96]. A guideline for the appropriate administration

Figure 29.03 Algoline® catheter — an example of a tunnelled externalised catheter for longterm intraspinal infusion (with permission from Medtronic)

Neuraxial Analgesia 481

programmable devices (Fig. 29.04). For patients with life expectancy of several months, a totally implantable infusion system would be more convenient and cost effective (Fig. 29.05). There are three types of intraspinal delivery techniques (Fig. 29.06):

Externalised system (percutaneous catheter with or without subcutaneous tunnelling) connected to an external infusion pump This is designed for short-term (days to weeks) use and the catheter can be placed either epidurally or intrathecally. Epidural placement is useful if a specific local anaesthetic block of the painful region is desired, but this requires a larger volume of infusion, which can easily be delivered via an external infusion pump. Otherwise intrathecal placement delivers equivalent analgesia with a much smaller dose and volume of drug. Pain of a diffuse nature is also better managed with intrathecal infusion especially using a hydrophilic opioid such as morphine. Debilitated cancer pain patients with limited life expectancy have been cared for at home for many weeks with this system supervised by the palliative care team. The main concerns are development of local infection at the exit site and catheter track infections leading to meningitis. The risk of infection is minimised by strict aseptic techniques when handling these systems. The use of tunnelled intrathecal catheters has not been associated with higher rates of complications than seen with externalised epidural and internalised catheters connected to subcutaneously implanted ports and reservoirs. Tunnelling provides stability and reduces the likelihood of unintentional withdrawal. However, infection, dislodgement, occlusion and kinking of the catheters remain potential problems [59, 97]. Both types of this system have also been used for short-term infusions in the management of exacerbation of chronic non-malignant spinal pain [59, 65] or as a trial screening process prior to pump implantation [25].

Figure 29.04 External pumps which can be connected to externalised catheter or injection ports for neuraxial infusions. Top: Baxter Infusor Port® with a fixed-rate balloon-type constant infusion device. Middle: Paragon® Pump with a constant pressure spring-loaded device driving the fluid filled reservoir bladder. Bottom: CADD® Pump, an electronic programmable device (with permissions from Baxter Healthcare Pty Ltd, Tuta Healthcare Pty Ltd and Smiths Medical International respectively).

482 Kok Eng KHOR

Figure 29.06 Schematic representation of implantable neuraxial access systems. 1. Externalized system with tunneled percutaneous catheter in epidural or intrathecal space. 2. Partially externalized system with implanted catheter (epidural on intrathecal) and subcutaneous injection port. 3. Totally implantable system with intrathecal catheter and infusion pump (programmable or fixed rate) Figure 29.05 Examples of totally implantable pumps for intrathecal infusion. Top: computerised programmable pump and catheter system (Synchromed II®) with programmer. Bottom: Fixed-rate gas-driven pump (Isomed®) (with permission from Medtronic)

Partially externalised system (implanted catheter with subcutaneous injection port) In this system, the tunnelled epidural or intrathecal catheter is connected to an injection access port (Port-A-Cath system), which is then implanted

subcutaneously. The port is accessed via a non-coring needle through which infusion can be commenced via an external pump or repeated injections given. Compared to the exteriorised catheter, this system permits more freedom of movement for the patient, is less easily dislodged and the infection rate is halved; it also allows patients to be cared for at home. It is preferable if longer-term use is anticipated (weeks to months) [22]. Totally implanted system (totally implanted catheter with infusion pump) This system consists of an implanted lumbar intrathecal catheter connected to an infusion pump

Neuraxial Analgesia 483

placed subcutaneously over the lower anterior abdominal wall. As the pump has a limited reservoir volume, intrathecal administration is the preferred method as this requires a smaller dose and volume of drug, thereby keeping refill time to a reasonable interval such as several weeks (rather than days). The medication is filled though a septum into the reservoir of the pump [53, 71]. Two main types of implantable infusion pumps are available: a computerised programmable pump, where the rate of infusion can be controlled, and a fixed-rate gasdriven pump (Table 29.02). There is no evidence to demonstrate the superiority of programmable pumps to fixed-rate infusion [73]. Implantable pumps have the advantage of a lower risk of infection and allow the patient more independence. However, the pump is more expensive and requires a more involved Table 29.02:

surgical procedure and is therefore generally reserved for patients with chronic non-malignant pain and cancer pain patients with several months’ (at least 3–6 months) life expectancy [71, 97].

Efficacy In general, patients with somatic nociceptive pain respond better to neuraxial opioids than other types of pain such as visceral, neuropathic and mixed nociceptive-neuropathic pain syndromes [68]. Neuropathic and mixed pain syndromes require higher doses of opioids [48, 68] and the addition of bupivacaine and clonidine [52, 55] for effective analgesia.

Programmable vs. fixed rate pump [17,74,77]

Constant flow pumps

Programmable pumps

Power source

• Vapour pressure from volatile liquids such as Freon gas.

• Battery powered motors

Flow control method

• Constant pressure exerted upon the fluid in the reservoir with a constant fluid flow, being controlled by a capillary flow restrictor.

• Peristaltic or microaccumulator

Advantages

• Simplicity and ease of care as no computer programmer is required • Lower cost • Longer potential lifetime utility • Larger reservoir and flow rate can incorporate more adjuvant drug volumes and can reduce number of refills

• Programmable rates and boluses allow individual tailoring to pain patterns. Potential for some patient control analgesia • Greater precision in dosing • Rate and drug dosage can be changed with programmer • All information stored in computer in pump and displayed on programmer

Disadvantages

• Lack of programmability: Dose can • More expensive only be changed by changing the • Limited battery lifespan and pump concentration of the drug in the needs to be replaced (every 4-5 reservoir. years) with additional cost for pump • Pump has no memory of drug replacement and surgery. information • Refills require use of programmer • Modest changes in pressure can alter and trained staff the flow rate of a vapour pressure driven pump (e.g. 2000m above sea level increase flow rate by about 10% and deep water diving at 2m depth decrease rate 10%). • Temperature changes affects flow rate (e.g. a 2˚C increase in body temperature increases flow rate by about 10%)

484 Kok Eng KHOR

Table 29.03

Selected published reports on use of neuraxial analgesia (studies from 1990) in cancer pain

IT-intrathecal; EPI-epidural; Morph-morphine; Hydromorph-hydromorphone; Bupi-bupivacaine; Clonclonidine; I/P-implantable pump; E/P-external pump; i-decrease; h-increase; sig- significant; P-patients; gpgroup; CMM-conservative medical management; >-greater than; 50% i in VAS) in 91% of P

Burton 2004 [15]

Retrospective IT and EPI case series (87P) infusion via E/P

Not stated

8 weeks

Reduction in proportion of patients with severe pain (VAS 7-10/10) from 86% to 17%. Significant i in drowsiness, mental clouding and oral opioid intake. No difference between IT & EPI infusions.

IT Morph/Bupi

486 Kok Eng KHOR

Authors: Year

Type of study Treatment (No. of Patients)

IT dosage (Morph)

Duration of treatment

Results

Smith 2005 [85]

Prospective randomised study (I/P 52P and CMM 91P)

Not stated

12 weeks

I/P gp- higher proportion of P achieved >20% reduction in pain & toxicity (57.9% vs 33.3%), greater mean pain reduction (47% vs 42%) and greater clinical success (82.5% vs 77.8%), reduction in toxicity score (66% vs 37%) compared to CMM gp Survival at 6 months: 52% in IDDS gp cf 32% in CMM gp

IT therapy via I/P vs CMM

In patients with cancer pain (see Table 29.03), neuraxial analgesia has been reported to provide good to excellent analgesia in 67–100% of patients [18, 37, 66]. Pain intensity scores, the proportion of patients with severe pain and oral supplemental analgesic use are also reduced accompanied by an improvement in function [15, 64]. Systemic opioid side effects and toxicity such as drowsiness and mental clouding are also significantly reduced [15, 86]. Compared with treatment with systemic analgesics, neuraxial analgesic therapy improves life expectancy [86]. However, 30% of patients have been shown to be unable to achieve sufficient pain relief with morphine alone. These patients required the addition of bupivacaine, which improved analgesia and enabled the use of a lower dose of morphine with a slower rate of subsequent dose increments [30, 93]. Despite the effectiveness of neuraxial opioids, some patients still require supplementation with oral opioids and adjuvants [97]. When the routes of administration are compared, both the intrathecal and epidural route have shown similar efficacy [15]. In patients with chronic non-malignant pain (see Table 29.04), 60–95% reported good to excellent pain relief with neuraxial analgesia in observational studies [7, 28, 39, 48, 52, 68, 74, 90]. Mean pain relief ranged from 30–60% [26, 28, 68, 77, 90, 100] with pain intensity scores decreasing between 1.5 to 5 points, and pain reducing from a severe to a moderate level [7, 90, 100, 101]. Pain reduction occurred in each of the sensory, affective and

evaluative domains [72]. Greater than 50% pain relief was reported in 30–44% of patients at longterm follow-up [7]. Most studies showed that 25– 74% of patients benefit from long-term continuous neuraxial opioid delivery with a very high patient satisfaction rating [77, 101, 105]. Pain relief has also been accompanied by documented reductions in oral medication intake (opioids, hypnotics, anxiolytics) [28, 39, 72, 77], objective measure of disability using the Oswestry pain score [26, 75], and depression, despair and distress. Substantial improvements in physical and functional activities and quality of life have also been documented [27, 39, 68, 77, 90, 100, 101]. However, some studies reported that patients continued to report high pain, disability and depression levels despite neuraxial analgesia with no significant change in work status [7, 14, 68, 77, 88]. In many cases, optimal outcome can only be achieved with a multidisciplinary treatment programme for which neuraxial analgesia is one component rather than the sole therapy [55, 61, 72]. Combining neuraxial analgesia with a cognitivebehavioural pain management programme helps patients learn how to manage their pain more effectively and has been shown to lead to significant improvements in affective distress, disability, selfefficacy and catastrophising [61]. There is also concern that tolerance can develop during long-term neuraxial infusion, limiting efficacy as seen with an initial high pain reduction

Neuraxial Analgesia 487

Table 29.04

Selected published reports on use of neuraxial analgesia (studies from 1990) with non-cancer pain Treatment & duration

IT Morph dosage; duration of treatment

Results

Retrospective Neuropathic 5P, case series (16P) Nociceptive 3P, mixed 8P

I/P (Morph ± Bupi) 28 months

1.7-8.9mg/day

Good to excellent pain relief 81%. Bupi used in 13P and improved analgesia in >2/3 of patients.

Hassenbusch 1995 [48]

Prospective Neuropathic case series (18P)

I/P (morphine) 2.4 years

12-34 mg/day

Fairly good to good pain reduction in 61% of P; failure of therapy in 39%.

Tutak 1996 [90]

Retrospective Failed back case series (26P) surgery (85%)

I/P(morphine) 23 months

9.3mg/day

Good to excellent pain relief in 77% of P. Average pain relief 59%; improvement in functionality of 50%.

Winkelmuller 1996 [101]

Retrospective case series (120P)

Neuropathic 28%, Nociceptive 11%, mixed 61%

I/P (Morph, buprenorphine) 3.4 years

4.7 ± 2.7mg

Pain reduction: nociceptive gp 48%, neuropathic gp 62%. Improvement in social function (51%), mood (55%) and QOL (81%). 92% of P satisfied with treatment and 74% benefited from IT opioid therapy.

Paice 1996 [88]

Retrospective survey of 35 physicians (289P)

Somatic 17% , visceral 8%, neuropathic 38%, mixed 37%

I/P with IT morphine (95%) 15 months

9.2 mg/day

82% of P h ADL, mean pain relief 61%, 10% of P RTW; Good to excellent pain relief in 95%.

Yoshida 1996 [105]

Retrospective Failed back case series (18P) surgery

I/P (Morph) 24 months

Not reported

25% of patients benefit from intrathecal morphine treatment

Authors: Year

Type of study (No. of patients)

Krames 1993 [[52]

Type of pain

488 Kok Eng KHOR

Treatment & duration

IT Morph dosage; duration of treatment

Results

Retrospective CNMP case series (36P)

I/P with IT morphine 20 months

7.7 mg/day

Pain reduction of 61%; i use of oral analgesics of 77%; functional improvement of 48%; 83% reported pain relief as good or excellent.

Anderson 1999 [7]

Prospective Neuropathic case series (30P) & mixed nociceptiveneuropathic pain

I/P (Morph / Hydromorph ± Bupi) 2 years

20.5 mg/day Bupi 1-5 mg/ day

Excellent or good outcome in 83%; 50% of patients ≥ 25% pain relief. No sig improvement in ADL and mood.

Willis 1999 [100]

Retrospective CNMP case series (29P)

E3/P (Opioids) 31 months

Not reported

Pain reduction 63%; improvement in level of activity 46%; improvement in performance activity of 54%

Brown 1999 [14]

Retrospective Chronic LBP case series (38P)

I/P (opioids) 50 months

18.6 mg/day

Continued report of high pain levels, disability, mild depression, low QOL, reduced physical function; 14% return to work, satisfaction 89%.

Rainov 2001 [74]

Prospective Chronic low case series (26P) back and leg pain (neuropathic or mixed nociceptiveneuropathic)

I/P (Morph ± Bupi ± Clon ± midazolam) 3.5 years

6.2mg ± 2.8mg

Excellent to good long term efficacy in 73%, sufficient pain relief in 23%, no relief in 4%.

Anderson 2001 [8]

Retrospective (37P)

I/P Hydromorph 10 months

3.2 mg (0.112.8mg)

Improved analgesia in 38% of P. No sig improvement in P who switched to Hydromorph due to Morph related sideeffects.

Authors: Year

Type of study (No. of patients)

Doleys 1998 [28]

Type of pain

Neuropathic pain & failed back surgery P who failed IT morphine

Neuraxial Analgesia 489

Treatment & duration

IT Morph dosage; duration of treatment

Results

Retrospective CNMP case series (88P)

I/P (diverse opioid ± bupivacaine ± clonidine) 36 months

15.3 mg/day

Mean pain relief 60%; h activity levels in 74%; i in oral opioid use; no change in work status; 88% satisfied with therapy.

Franco Gay 2002 [39]

Retrospective Neuropathic case series (39P) 22P Nociceptive 17P

I/P (Morph ± Bupi ± Clon) 1.5 – 6.5 years (2.2 years)

2mg/day

Good to excellent pain relief 78%, improved activity 31%; Use of oral opioids i50%; 91% satisfied with therapy.

Deer 2004 [23]

Prospective case Chronic LBP series (136P) of diverse aetiologies

I/P 12 months

Dose not stated

Pain ratings i 47% for back pain & 31% for leg pain; idisability score in > 65%; >80% of patients satisfied with therapy.

Thimineur 2004 [88]

Prospective controlled study of 3 matched gps (I/P 38P, nonI/P gp 31P, new referred P 41P)

I/P (opioid ± Clon)

Morph 10.8mg/ day Hydromorph 13.5mg/day

I/P gp showed sig improvements in pain intensity, mood, function & oral analgesic use compared to baseline. Non-I/P gp worsened. Severity of pain and symptoms of I/P gp worse than new referred gp.

5.33mg @12 mths

25% reduction in average pain intensity (1.3-1.8 points)

Authors: Year

Type of study (No. of patients)

Roberts 2001 [77]

Type of pain

CNMP

Non-I/P and new referred P – multidisciplinary treatment (opioids, injection, physical & psychological) 3 years

Du Pen 2006 [29]

Retrospective Diverse case series (24P)

I/P Hydromorph (8P started on Hydromorph, 16P from sideeffects to Morph) 1.3 years

490 Kok Eng KHOR

Authors: Year

Type of study (No. of patients)

Type of pain

Treatment & duration

IT Morph dosage; duration of treatment

Results

Doleys 2006 [27]

Retrospective controlled study of 3 matched gps ( I/P gp 50P; Rehab gp 40P; Oral opioid gp 40P)

Chronic LBP “failed back surgery”

I/P (Morph 21mg/day) Oral opioids (Morph 99mg/ day) Rehab gp – 4 weeks residential programme

To 21mg/day

Pain reduction highest in I/P gp (35.5%) cf 8% for Rehab and 8.5% for oral opioids; Patient satisfaction highest for Oral opioid gp (97%), I/P (88%) and least for Rehab 51%); Patients continued to experience sig levels of pain, disability and i QOL despite overall improvement of 50-60% and high levels of satisfaction with treatment.

4 years

which decreases over time [101]. The incidence of tolerance ranges from 4–30%, but it does not lead to discontinuation of therapy nor limit its effectiveness and is usually resolved by changing to an alternative opioid or use of adjunctive agents such as clonidine and bupivacaine [7, 77, 95, 101]. At the start of therapy, there is usually a relatively rapid escalation of dose in the first 6 months, followed by a 2- to 4fold increase in dose from 6 months to 24 months and thereafter the dose generally remains stable [68, 90, 101]. However, the variation in dose is often large because of physician-imposed limits due to concern about hyperalgesia, side effects, the need to reduce frequent pump refills and differences in opioid sensitivity of neuropathic and nociceptive pain syndromes.

Cost-Effectiveness A cost analysis comparison of intrathecal analgesia via an implantable programmable pump

compared with conventional medical treatment for the management of failed back surgery showed intrathecal therapy to be cost effective at 22 months. The cost of oral/transdermal opioid exceeded that of intrathecal opioids at 25 months [45]. In patients with cancer pain, the implantable programmable opioid pump becomes more costeffective beyond 3 months of treatment when compared with an externalised epidural catheter delivery via an external pump and subcutaneous or intravenous opioid infusion [10]. Although the initial cost of surgical implantation of a pump is higher, maintenance costs remain relatively stable over time irrespective of the treatment duration or dosage escalation and are significantly lower than other routes of administration. Cost analysis indicates that intrathecal delivery is the most cost-effective route of opioid administration for patients who require long-term management of cancer or non-malignant pain.

Neuraxial Analgesia 491

Table 29.05

Pharmacological adverse events with neuraxial opioid delivery [1,5,32,33,63,67,68,89,101]

Adverse event

occurrence

Frequency

Causes

Management

Pruritus

Early; dose related and reduce with repeated doses

13-38%

Central causes with interaction with trigeminal nucleus & initiation of itch reflex

Naloxone and antihistamine

Nausea & vomiting

Early; dose related and tolerance develops

12-37%

Cephalad migration of opioid in CSF to interact with opioid receptors in area postrema.

Initiate opioid therapy at low dose (e.g. morphine 0.5mg/day) and increase slowly; antiemetic agents

Urinary retention

Early; high risk in older males with prostatomegaly

5-44%

Bladder detrusor muscle relaxation from inhibition of parasympathetic outflow caused by opioid receptors in sacral spinal cord

Bladder catheterization; cholinomimetic drugs e.g. bethanechol; low dose naloxone

Constipation

Early

0-52%

Opioid receptor induced reduction in gastrointestinal motility

Dietary changes; laxatives and stool softeners

Respiratory depression

Early; dose related; increased risk in the opioid naïve, advanced age, use of sedatives

0-4%

Cephalad migration of opioid in CSF to respiratory centre

Regular monitoring, oxygen, stop and subsequent reduction in dose of opioid, naloxone infusion if severe

Sedation / cognitive impairments / nightmares, paranoia, anxiety, euphoria (rarer)

Early; dose related and tolerance develops

0-4%

Central nervous system depressant

Start opioid therapy at low dose and allow tolerance to develop; haloperidol for persistent confusion and delirium

Sexual dysfunction (reduced libido, impotence, dys/ amenorrhoea)

Late

4-49%

Hypothalamicpituitary axis suppression causing hypoganadotropic hypogonadism (suppression of GnRH, LH, testosterone, oestrogen

Hormonal replacements; reduction in dose of opioid

Weight gain

late

5-10%

Cause unknown

Reduction or cessation of IT opioid

Oedema

Late and persist; 6-17% risk with preexisting leg oedema and venous insufficiency

Cause unknown – may be related to hormonal changes

Reduction in opioid dose; opioid rotation; may have to cease therapy

492 Kok Eng KHOR

Adverse event

occurrence

Frequency

Causes

Management

Sweating

Late and persist

2-9%

Cause unknown

Unknown

Opioid induced hyperalgesia

Early to late

uncommon

Opioid activated pronociceptive systems including NMDA receptor activation

Reduction or cessation of IT opioid, opioid rotation, NMDA antagonist

Risks and Complications Risks and complications related to intraspinal administration of analgesic agents can be classified as: 1. Pharmacological side-effects 2. Medical/surgical complications 3. Device-related complications.

Pharmacological side effects Neuraxial opioids The adverse effects of neuraxial opioids (Table 29.05) are similar, although less severe than those of systemic administration and usually reduce over time. They can be minimised by starting at a low dose, slow titration to effect, prompt recognition and management [63]. Some side effects such as endocrine abnormalities, sexual dysfunction, sweating and peripheral oedema develop over time and may persist [77, 101]. Other less common side effects reported include paranoia, hyperalgesia, myoclonus, Ménière’s-like symptoms, nystagmus and polyarthralgia [97]. Neuraxial bupivacaine Side effects of bupivacaine result from its anaesthetic effects at the spinal level and are dose-related. They include paraesthesias, sensorimotor block, hypotension, urinary retention and diarrhoea. Studies of cancer patients show them to occur more frequently at intrathecal doses of greater than 30–45 mg/day and in epidural infusion at concentrations above 0.25–0.35% [52, 80, 82, 93]. Neuraxial clonidine The most common side effects of clonidine are lethargy, impotence, hypotension, bradycardia and sedation. Side effects are often well tolerated even at epidural doses of up to 720–1680 mcg/day and intrathecal doses of up to 960 mcg/day. There is

a risk of severe rebound hypertension with abrupt cessation of intrathecal clonidine [31, 44].

Medical/surgical complications Bleeding Bleeding related to the operative wound is uncommon and the main concern is spinal haematoma leading to spinal cord compression, which is a neurosurgical emergency. Patients should, therefore, be monitored for development of severe back pain and neurological deficits. Infection Infection can occur along the superficial or deep catheter tract, pump site or within the intraspinal space. Patients who are at risk include those who are immunocompromised or have poor wound healing, such as in AIDS and diabetes. The incidence of local infection is reported to be 0–9% and is usually caused by Staphylococcus aureus, Staphylococcus epidermidis and Gram-negative bacilli. Risk of infection with short-term catheter use is very low; it is more common with externalised long-term catheters and there is no difference between intrathecal and epidural placements. Mild infections can be treated with oral antibiotics, but severe infections require intravenous antibiotics. Persistent and worsening infection despite systemic antibiotic therapy may necessitate the removal of the entire delivery system [35, 36, 63]. The incidence of meningitis is low and was reported in some series to be 1% [15, 51]. For infections involving the device components tracking to the CNS, prompt removal of all the infected components and concomitant administration of parenteral antibiotics is recommended. For isolated CSF infection, intrathecal infusion of preservativefree antibiotics through the pump has been described [35]. Occurrence of epidural abscesses from Staphylococcus aureus and Gram-negative

Neuraxial Analgesia 493

bacilli have been reported with long-term epidural catheters [15, 97]. To reduce the risk of infection, careful patient selection and preventative measures are recommended; the latter include the use of perioperative intravenous antibiotics during device implantation and attention to a meticulous sterile technique during implantation and refilling. For externalised catheters, the use of antimicrobial dressing such as chlorhexidine and bacterial filters reduces bacterial colonisation. Bacterial filters maintain their function for at least 60 days and their frequent change can lead to a higher incidence of catheter hub colonisation. Tunnelling the catheter subcutaneously to exit distally to reduce the incidence of catheter infection has not been proven [16, 22, 97]. Consultation with an infectious disease physician is important in cases of severe intraspinal and local infections.

Seroma A serosanguinous fluid collection in the pump pocket may develop and is generally self-limiting but can be irritating especially if large. Small swellings are left alone but can be aspirated especially before the pump is refilled. For recurring swellings, a pressure bandage applied after aspiration will often help to reduce the swelling [18]. Cerebrospinal fluid leaks Leakage of CSF occurs because incomplete tissue sealing at the insertion site allows fluid to track back to the catheter anchor site causing a soft fluctulant swelling around the lumbar area. It can also track to the pump pocket resulting in CSF hygromas. This complication may be reduced by an additional suture on to the fascia to create a tighter tissue seal around the catheter. Usually, the swelling resolves over a few weeks, but persistent cases may require aspiration and re-suturing over the catheter exit site [36, 63]. Postdural puncture headache Incidence of postdural puncture headache is reported to range from 1–30% and may result from CSF leakage around the catheter and loss of CSF during the implantation procedure. In most cases, the headache is mild to moderate and settles within a few days; if severe and persistent, a blood patch under fluoroscopy can be performed [18, 63].

Neurological injury Implantation of the catheter into the epidural and intrathecal space can cause injury to the nerve roots or the spinal cord leading to radiculitis, myelitis, paresis, loss of bowel or bladder control and/or neuropathic pain. Entry of the catheter into the spinal cord has been reported. Patients present with early onset neurological deficits which are worsened by the intramedullary infusion. The infusion should be ceased and a thorough and early investigation carried out with magnetic resonance imaging (MRI) or a computed tomography myelogram. If confirmed, the catheter is removed. Outcomes range from resolution to residual neurological deficits with post-traumatic syrinx formation [42, 50, 83].

Device-related complications Catheter complications The catheter is responsible for most of the delivery system complications and these occur in 16.5% to 34.6% of patients [51 90, 101]. Complications are usually related to the implantation procedure rather than to the inherent qualities of the catheter and highlight the need for careful surgical technique in reducing the rate of complications [36, 38]. Catheter complications include dislodgement or migration (~4–6%), occlusion or kinking (~2%), leakage (~6%), fracture or breaks (~4%) and disconnection (~1–2%). The usual site of catheter breakage is at the spinal entry site; the distal segment can migrate, resulting in a free-floating catheter fragment in the CSF. Catheters can also be damaged by needle puncture during pump refill and during a catheter revision procedure [38, 51]. The patient often complains of sudden loss of analgesia, inconsistent analgesia or drug withdrawal symptoms. Algorithms for the investigation of patients presenting with sudden loss of analgesia to locate the source of the mechanical problems with the delivery system have been suggested (Table 29.06) and remedial actions can be taken to repair or replace the catheter. Catheter fibrosis Both epidural and intrathecal catheters can induce a non-specific inflammation causing a fibrotic reaction that envelops the catheter tip after 1 to 2 weeks. The incidence of this epidural fibrosis is between 0.5% and 19% and appears to be higher than in the intrathecal space. Catheter fibrosis can

494 Kok Eng KHOR

Table 29.06

Investigations for loss of neuraxial analgesia thorough implantable pump Procedure

Lack of Efficacy: tolerance change in pathology development of new pathology problem with drug delivery device

Evaluation

Check neurological function Check Pump

Adequate amount of medication in reservoir Ensure programmed properly (programmable pump) Check battery status

Pump rotor study

Pump telemetry failure

Evaluate Catheter -X-ray thoracolumbar spine (AP & lateral) and pump

view catheters to check that it is not broken, dislodged or migrated

-aspirate from side-port to obtain CSF

check integrity of system, obstruction, kinks, dislodgement, migration from IT space, break in catheter

fluoroscopic study with contrast

shows integrity of system, leaks, disconnection, flow of CSF

result in pain and difficulty with injection, backleakage from the catheter at the insertion point and can cause spinal cord compression [97].

Intrathecal granuloma Development of an intradural-extramedullary chronic granulomatous mass that envelops the tip of the catheter can occur with long-term infusion. Granulomas may be asymptomatic but over time may expand and lead to spinal cord compression. A prospective study showed a prevalence of 3% of which 80% were asymptomatic [26]. Patients can present with loss of analgesia, frequent need for dose escalation, new onset radicular pain or paraesthesias and slowly progressive neurological deficits. Although granuloma formation cannot be prevented, the risk can be reduced by using as low a dose as possible (e.g. 4 x 109/L). Furthermore, there should not be evidence of spinal cord compression when other treatment — external radiotherapy or surgery — would be a better treatment choice.

Samarium-153 Samarium-153 forms a complex with ethylenediaminetetramethylene phosphonic acid to become 153Sm-EDTMP. It acts similarly to 99mtechnetium (99mTc-methylene diphosphonate) and has distribution equivalent to a technetium bone scan. Response rates are between 62–84%. Pain relief is obtained within 2 to 3 weeks and pain control can last for up to 4 months [11, 60, 65]. The main toxicity is myelosuppression, which is generally mild and transient, and re-treatments have been shown to be safe and effective [34].

Spinal cord compression usually occurs at late stages of metastatic cancer. More than half of patients with spinal cord compression have primary cancers of breast, lung, nasopharynx and prostate. Other less frequent causes include multiple myeloma, lymphoma, melanoma and renal cell carcinoma. Nowadays, with advancement in treatment and prolonged survival, we are beginning to see spinal cord compression arising from cancers that are not so well known for bone metastasis, e.g. colorectal cancers. The thoracic spine is the most common location of spinal cord compression and is followed by lumbar and cervical spine. In the majority of patients, spinal cord compression is caused by extradural metastases. Occasionally, it can be due to epidural compression from intraspinal metastases or direct extension through the intervertebral foramina from a paraspinal mass.

Rhenium-186 Rhenium-186 forms a complex with 1,1 hydroxyethylidene diphosphonate to become 186Re-HEDP. Rhenium-188 is an isotope of Re186 and after forming 188Re-HEDP, it has similar bio-distribution and radiation dosimetry. A study comparing Sr-89 to 186Re-HEDP in 50 breast cancer patients demonstrated similar response rates (84% and 92%) between the two isotopes but 186Re-HEDP had earlier onset of pain relief and quicker marrow recovery [62]. Re-treatment is effective with 188Re-HEDP [44].

Patient selection Patients considered suitable for bone-seeking radionuclides are those with symptomatic multiple or widespread bone metastases which are positive on bone scan. There should be adequate renal function and bone marrow reserve (platelets >60

Special Painful Conditions Spinal cord compression Spinal cord compression is an oncological emergency as the outcome of therapy depends on the degree of neurological impairment at the start of treatment. In one review, when patients were ambulatory at the start of radiotherapy, 79% remained ambulatory at the end of treatment, while only 3% of patients became ambulatory if they presented with paralysis.

Back pain is often the first symptom. This can precede the neurological deficits by weeks or months. The pain can be localised in the spine, be radicular or both. Localised pain is constant, dull and progressive. Radicular pain is intermittent and shooting in nature. Limb weakness can be a presenting symptom. The weakness is most obvious at the proximal muscles and is often accompanied with sensory disturbances which begin distally and spread upwards. Symptoms of autonomic dysfunction like urinary retention and constipation are usually late findings and are associated with poor prognosis.

532 Rico K.Y. LIU, Arthur YUE, Gordon K.H. AU

The key to successful management of spinal cord compression is early diagnosis. This involves accurate neurological history and physical examination followed by appropriate investigations. Metastases to bone can be demonstrated in plain radiographs. However, plain radiographs may be normal in patients with epidural compression. A magnetic resonance imaging (MRI) scan is the investigation of choice. It is the most sensitive and specific investigation, and can differentiate spinal cord compression due to malignancy from epidural abscess, epidural hematoma and disc herniation. The goals of treatment for spinal cord compression are preservation or recovery of neurological functions, local tumour control, stabilisation of the spine and pain control. The initial treatment for all patients is corticosteroids, which reduce spinal oedema and improve neurological function. Dexamethasone is the steroid most widely used. It should be started as soon as there is suspicion of spinal cord compression. The conventional dosage is 4 mg three to four times a day. Definitive treatment is surgery, radiation therapy or both. There are no randomised data to indicate the superiority of surgery versus radiation. However, surgery has a more immediate effect in achieving neurological improvement. Surgical decompression should be considered for patients with no histological diagnosis or radioresistant tumours, acute onset paraplegia, spinal instability or complete collapse of vertebral body and previous radiotherapy to the site of compression. Traditional decompressive laminectomy has a low success rate due to poor exposure of tumour. As most spinal cord compression results from tumours positioned anteriorly or anterolaterally, an anterior decompression with vertebral body resection followed by spinal stabilisation is more appropriate. However, this approach is a major procedure and patients selected for this procedure should be in good general condition or have a reasonable life expectancy [39]. In recent years, a new treatment, vertebroplasty, has been introduced where resin is injected into the affected vertebral body under X-ray guidance to provide structural support and prevent further collapse, thus relieving pain and preventing further neurological deficits. Radiation therapy is most suitable for patients with gradual onset and progression of symptoms with no spinal instability. Radiation therapy reduces pain in

70% of patients and improves motor function in 45–60% of patients. Treatment outcome depends on the relative radiosensitivity of malignancy and neurological status of the patient at the start of radiotherapy. In a prospective trial, treatment outcome was superior for radiosensitive tumours such as lymphoma and myeloma compared with less radiosensitive tumours such as renal cell carcinoma and hepatoma. Treatment outcome is also more superior if patients are able to ambulate at the start of treatment compared with outcome in paraplegic patients [35]. In general, the treatment portal includes the area of compression as evident on plain X-ray plus two vertebral bodies above and below and a width of 8 cm or more depending on the width of the tumour mass as visualised on imaging studies. With the advent of MRI and its more accurate imaging of the affected areas, a smaller margin of one vertebral body above and below the affected area can be used. This helps reduce the side effects from radiotherapy and also preserves more marrow, which may be needed if future chemotherapy is planned. The optimal dose and fractionation schemes have not been determined. The most commonly used schedules in this part of the world are 30 Gy in 10 fractions or 28 Gy in seven fractions over 1 to 2 weeks with a single posterior field. Chemotherapy may be an effective treatment for selected patients with very chemosensitive tumours such as small cell carcinoma of the lung, and some lymphomas. It may be considered in combination with other treatment modalities such as radiotherapy. In general, however, for most other tumours, chemotherapy is not used as the first treatment when pain control is the primary goal. Since outcome of treatment for spinal cord compression is dependent on early treatment when there is minimal neurological deficit, prophylactic irradiation should be considered for high-risk patients who have back pain and positive bone scans.

Brain metastases Brain metastases occur in 20–40% of patients with cancer. The neurological symptoms can have a profound effect on quality of life. The natural history of untreated brain metastases is progressive neurological deterioration with a median survival of 1 to 2 months. In Hong Kong, the most common sources of brain metastases are from the lung and

Radiotherapy in the Management of Pain in Cancer Patients 533

breast. Other less common tumours are colorectal carcinoma, renal cell carcinoma and melanoma. The majority of brain metastases are found in the cerebral hemisphere and they are commonly multiple. Most patients are symptomatic. The symptoms are usually insidious in onset and develop over a few weeks. Headache is the most common symptom. It is usually mild, diffuse and can be bifrontal. It is also more common in patients with multiple metastases and those with metastases in the posterior cranial fossa. Headache can be due to raised intracranial pressure, which is commonly worse in the mornings and can be aggravated by manoeuvres which increase the intracranial pressure such as coughing. Other common symptoms are focal weakness, cognitive dysfunction and seizures. The diagnosis of brain metastases is established by computed tomography (CT) or MRI, the latter being more sensitive. Brain metastases appear as circumscribed lesions with homogeneous enhancement after contrast infusion. They are commonly surrounded by oedema and may cause mass effect. In patients with no known primary or other systemic metastases or in patients who present with a solitary brain lesion following a long disease-free interval, causes other than brain metastases have to be considered. These include abscess, cerebral infarct or haemorrhage, radiation necrosis and glioma. Biopsy of the brain lesion is recommended. The goal of treatment is palliative. Corticosteroids result in symptoms improvement in 60–75% of patients with brain metastases. The mechanism of action is not completely understood. Amelioration of symptoms is most probably due to reduction of oedema. Dexamethasone 4 mg three to four times daily is the common dosage. Radiation therapy is the treatment of choice for most patients with brain metastases. The response rate ranges from 70–90%. Improvement in neurological function depends on the patient’s neurological function at the time of irradiation. The more severe the neurological impairment, the less chance there is for significant improvement. Most patients are treated with whole brain irradiation. Short courses of radiation of 20 Gy in 1 week, or 30 Gy in 2 weeks, are generally as effective as more prolonged courses [6]. “Ultrarapid fractionation” like a

single fraction of 10 Gy gives a shorter duration of control, and more severe acute toxicities, when compared with 30 Gy in 10 fractions. Whole brain irradiation increases the median survival time to 3 to 6 months. Steroid cover, such as dexamethasone, should always be given to patients with symptomatic or large, cerebral metastases before radiotherapy is started. This reduces the amount of acute toxicity which may occur in the early days of treatment resulting from oedema. Patients with a solitary brain metastasis with good performance status and controlled primary lesion should be considered for surgical resection. Phase 3 studies show a survival benefit for surgical resection in selected patients [45]. The survival of the surgical group is 10 months. Surgical resection is followed by whole brain irradiation, which aims at eradicating micrometastases that may not show up on imaging. Stereotactic radiosurgery is a newer method which delivers very localised but intense irradiation using a linear accelerator or multiple cobalt-60 sources. In highly selected patients, it may be a substitute to surgery. Generally, it is used to treat lesions less than 3 cm in diameter. Results from uncontrolled studies have shown that the local control rate with radiosurgery is comparable to conventional surgery [60]. To date, the experience from radiosurgery still does not allow us to form a conclusion regarding its use in the treatment of metastatic brain disease. Radiation therapy can cause morbidity to patients. The side effects are nausea, vomiting, headache and alopecia. In some patients, there may be worsening of the neurological state; this could be due to increased capillary permeability caused by radiation. Steroids during therapy may minimise these complications.

Nerve plexus metastases Metastatic plexopathy often causes significant pain and neurological disability in cancer patients. The commonly involved nerve plexuses are the brachial and lumbosacral plexus. Pain is produced when these structures are infiltrated by tumour or compressed by fibrosis after radiation therapy to adjacent structures. Pain tends to be less prominent in radiation-induced plexopathies than in tumourrelated ones. Brachial plexopathy in cancer patients is usually the result of metastatic cancer in axillary or cervical

534 Rico K.Y. LIU, Arthur YUE, Gordon K.H. AU

lymph nodes or from superior sulcus lung tumours. Most metastatic tumours affect the lower division of the brachial plexus. Pain usually begins in the shoulder and radiates into the medial forearm and arm and into the fourth and fifth digits (C8 or T1 distribution).Weakness and sensory loss may follow. The lumbosacral plexus may be invaded by colorectal tumours, gynaecological tumours, lymphoma and sarcoma. Pain is usually felt in the lower abdomen, buttock and leg. This is followed by sensory deficits and weakness weeks or months later. Pelvic CT or MRI scans may provide the diagnosis and allow definition of radiation portals.

Pain relief can be achieved by radiation therapy. Symptomatic relief occurs in 83% of cases where pain is due to recurrent tumour [29]. For pelvic mass, anteroposterior portals are often used. A three-field technique can be used for a pre-sacral mass with anterior bladder and some bowel sparing. Single anterior or opposing fields can be used for supraclavicular or axillary massses. A radiation regimen of 30 Gy in 10 fractions over 2 weeks is commonly used. Chemotherapy may be useful for some previously irradiated patients such as patients with breast carcinoma or lymphoma. Equally important is the role of analgesia in management of painful metastatic plexopathy as radiation therapy may take some time to be effective.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

Allen KL, Johnson TW, Hibbs GG. Effective bone palliation as related to various treatment regimens. Cancer 1976;37(2):984–7. Arcangeli G, Micheli A, Arcangeli G, et al. The responsiveness of bone metastases to radiotherapy: The effect of site, histology and radiation dose on pain relief. Radiother Oncol 1989;14(2):95–101. Bates T. A review of local radiotherapy in the treatment of bone metastases and cord compression. Int J Radiat Oncol Biol Phys 1992;23:217–21. Blitzer PH. Re-analysis of the RTOG study of the palliation of symptomatic osseous metastasis. Cancer 1985;55:1468– 72. Bonica JJ. Cancer pain. In Bonica JJ, ed. Pain. New York: Raven Press, 1980:335–62. Borgelt B, Gelber R, Kramer S, et al. The palliation of brain metastases: Final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1980;6(1):1–9. Brescia FJ, Portenoy RK, Ryan M, et al. Pain, opioid use and survival in hospitalised patients with advanced cancer. J Clin Oncol 1992;10:149–55. Brescia FJ. Pain management issues as part of the comprehensive care of the cancer patient. Semin Oncol 1993;20(Suppl A):48–52. Carter RL. Patterns and mechanisms of bone metastases. J Royal Soc Med 1985;78(Suppl 9):2–6. Cheung A, Driedger AA. Evaluation of radioactive phosphorus in the palliation of metastatic bone lesions from carcinoma of the breast and prostate. Radiology 1980;134(1):209–12. Collins C, Eary JF, Donaldson G, et al. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: A phase I/II trial. J Nucl Med 1993;34:1839–44. Coia LR, Hanks GE, Martz K, et al. Practice patterns of palliative care for the United States 1984-1985. Int J Radiat Oncol Biol Phys 1988;14(6):1261–9. Cole DJ. A randomised trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. Clin Oncol 1989;1:59–62. Cornforth MN, Bedford JS. A quantitative comparison of potentially lethal damage repair and the rejoining of interphase chromosome breaks in low passage normal human fibroblasts. Radist Res 1987;111:385–405. Crellin AM, Marks A, Maher EJ. Why don’t British radiotherapists give single fractions of radiotherapy for bone metastases? Clin Oncol 1989;1(2):63–6. Danjoux CE, River WD, Fitzpatrick PJ. The acute radiation syndrome. Clin Radiol 1979;30:581–4. Donnelly S, Walsh D. The symptoms of advanced cancer. Semin Oncol 1995;22:67–72. Ben-Josef E, Shamsa F, Williams AO, et al. Radiotherapeutic management of osseous metastases: A survey of current pattern of care. Int J Radiat Oncol Biol Phys 1998;40(4):915–21. Fidler IJ, Radinsky R. Genetic control of cancer metastasis. J Natl Cancer Inst 1990;82:166–8.

Radiotherapy in the Management of Pain in Cancer Patients 535

20. Foley KM. Pain syndromes in patients with cancer. In Bonica JJ, Ventafridda V, eds. Advances in Pain Research and Therapy, Vol 2. New York: Raven Press, 1979:59–75. 21. Foley KM. The treatment of cancer pain. N Eng J Med 1995;313:84–94. 22. Ford HT, Yarnold JR. Radiation therapy — pain relief and recalcification. In Stoll BA, Parbhoo S, eds. Bone Metastases: Monitoring and Treatment. New York: Raven Press, 1983:343–54. 23. Front D, Chneck SO, Frankel A. Bone metastases and bone pain in breast cancer. Are they closely related? JAMA 1979;242:1747–8. 24. Fryer CJH, Fitzpatrick PJ, Rider WD, et al. Radiation pneumonitis: Experience following a large single dose of radiation. Int J Radiat Oncol Biol Phys 1978;4:931–6. 25. Gilbert HA, Kagan AR, Nussbaum H, et al. Evolution of radiation therapy for bone metastases: Pain relief and quality of life. Am J Roentgenol 1977;129:1095–6. 26. Grubbe E. Priority in therapeutic use of X-rays. Radiology 1933;21:156–62. 27. Hazra T, Giri S. Prophylactic pelvic girdle irradiation in the treatment of prostatic carcinoma. Int J Radiat Oncol Biol Phys 1981;7:817–9. 28. Hoskin PJ, Price P, Easton D, et al. A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain. Radiother Oncol 1992;23(2):74–8. 29. James RD, Johnson RJ, Eddleston B, et al. Prognostic factors in locally recurrent rectal carcinoma treated by radiotherapy. Br J Surg 1983;70:469–72. 30. Jensen NH, Roesdahl K. Single dose irradiation of bone metastasis. Acta Radio Ther Phys Biol 1976;15:337–9. 31. Madsen E. Painful bone metastases: Efficacy of radiotherapy assessed by the patients: A randomised trial comparing 4 Gy x 6 versus 10 Gy x 2. Int J Radiat Oncol Biol Phys 1983;9:1775–9. 32. Malawer MM, Delanet TF. Treatment of cancer metastatic to bone. In DeVita VT, Hellman S, Rosenberg SA. Principles and Practice of Oncology, 4th edn. Philadelphia: JB Lippincott, 1993:2225–44. 33. Malmberg I, Persson U, Ask A, et al. Painful bone metastases in hormone refractory prostate cancer: Economic costs of strontium-89 and/or external radiotherapy. Urology 1997;50:747–53. 34. Maini CL, Bergomi S, Romano L, et al. 153Sm-EDTMP for bone pain palliation in skeletal metastases. Eur J Nucl Med Mol Imaging 2004;31(Suppl 1):S171–8. 35. Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: Final results of prospective trial. Int J Radiat Oncol Biol Phys 1995;32:959–67. 36. McEwan AJ, Amyotte GA, McGowan DG, et al. A retrospective analysis of the cost effectiveness of treatment with Metastron in patients with prostate cancer metastatic to bone. Eur Urol 1994;26(Suppl 1):26–31. 37. Mehta MP, Rozental JM, Levin AB, et al. Defining the role of radiosurgery in the management of brain metastases. Int J Radiat Oncol Biol Phys 1992;24(4):619–25. 38. Mithal NP, Needham PR, Hoskin PJ. Retreatment with radiotherapy for painful bone metastases. Int J Radiat Oncol Biol Phys 1994;29:1011–14. 39. Moore AJ, Utter D. Anterior decompression and stabilization of spine in malignant disease. Neurosurgery 1989;24,713– 7. 40. Needham PR, Mithal NP, Hoskin PJ. Radiotherapy for bone pain. J R Soc Med 1994;87:503–5. 41. Nielsen OS, Munro AJ, Tannock IF. Bone metastases: Pathophysiology and management policy. J Clin Oncol 1991;9:509–24. 42. Núñez MI, McMillan TJ, Valenzuela MT, et al. Relationship between DNA damage, rejoining and cell killing by radiation in mammalian cells. Radiother Oncol 1996;39(2):155–65. 43. Onufrey V, Mohiuddin M. Radiation therapy in the treatment of metastatic renal cell carcinoma. Int J Radiat Oncol Biol Phys 1985;11:2007–9. 44. Palmedo H, Manka-Waluch A, Albers P, et al. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: Randomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. J Clin Oncol 2003;21:2869–75. 45. Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322(8):494–500. 46. Portenoy RK, Miransky J, Thaler HT, et al. Pain in ambulatory patients with lung or colon cancer. Prevalence, characteristics, and effect. Cancer 1992;70(6):1616–24. 47. Porter AT, McEwan AJ, Powe JE, et al. Results of a randomized phase III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys 1993;25(5):805–13. 48. Poulsen HS, Nielsen OS, Klee M, et al. Palliative irradiation of bone metastases. Cancer Treat Rev 1989;16(1):41–8. 49. Poulter CA, Cosmatos D, Rubin P, et al. A report of RTOG 8206: A phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of systematic osseous metastases. Int J Radiat Oncol Biol Phys 1992;23(1):207–14.

536 Rico K.Y. LIU, Arthur YUE, Gordon K.H. AU

50. Powers WE, Ratanatharathorn V. Palliation of bone metastases. In Perez CA, Brady LW, eds. Principles and Practice of Radiation Oncology, 3rd edn. Philadelphia: Lippincott-Raven Publishers, 1997:2199–217. 51. Price P, Hoskin PJ, Easton D, et al. Low dose single fraction radiotherapy in the treatment of metastatic bone pain: A pilot study. Radiother Oncol 1988;12(4):297–300. 52. Price P, Hoskin PJ, Easton D, et al. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Radiother Oncol 1986;6(4):247–55. 53. Qasim MM. Half body irradiation (HBI) in metastatic carcinomas. Clin Radiol 1981;32: 215–9. 54. Quilty PM, Kirk D, Bolger JJ, et al. A comparison of the palliative effects of strontium-89 and external beam radiotherapy in metastatic prostate cancer. Radiother Oncol 1994;31:33–40. 55. Rasmusson B, Vejborg I, Jensen AB, et al. Irradiation of bone metastases in breast cancer patients: A randomised study with 1 year follow up. Radiother Oncol 1995;34(3):179–84. 56. Rate WR, Solin LJ, Turrisi AT. Palliative radiotherapy for metastatic malignant melanoma: Brain metastases, bone metastases and spinal cord compression. Int J Radiat Oncol Biol Phys 1998;15:859–64. 57. Rowland CG. Single fraction half body radiation therapy. Clin Radiol 1979;30:1–3. 58. Salazar OM, Rubin P, Hendrickson FR, et al. Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Final Radiation Therapy Oncology Group report. Cancer 1986;58(1):29–36. 59. Scarantino CW, Caplan R, Rotman M, et al. A phase I/II study to evaluate the effect of fractionated hemibody irradiation in the treatment of osseous metastases: RTOG 82-22. Int J Radiat Oncol Biol Phys 1996;36(1):37–48. 60. Serafini AN, Houston SJ, Resche I, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: A double-blind placebo-controlled clinical trial. J Clin Oncol 1998;16:1574–81. 61. Schocker JD, Brady LW, Risch VR. Radiation therapy of bone metastases. The Hahnemann experience. In Weiss L, Gilbert HA, eds. Bone Metastases. Boston: Hall, 1981:436–42. 62. Sciuto R, Festa A, Pasqualoni R, et al. Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients. Br Cancer Res Treat 2001;66:101–9. 63. Senn HJ. Supportive and palliative care in cancer patients. In ESMO Education Book. Vienna: ESMO, 1996:131–4. 64. Strickland P. Complications of radiotherapy. Br J Hosp Med 1980;23:552–65. 65. Tian JH, Zhang JM, Hou QT, et al. Multicentre trial on the efficacy and toxicity of single-dose samarium-153-ethylene diamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases in China. Eur J Nucl Med 1999;26(1):2–7. 66. Tong C, Gillick L, Hendricksen FR. The palliation of symptomatic osseous metastases: Final results of the study by the Radiation Therapy Oncology Group. Cancer 1982;50:893. 67. Turner R. Principles of palliative care. In Horwich A, ed. Oncology: A Multidisciplinary Textbook, 1st edn. London: Chapman & Hall Medical, 1995:199–211. 68. Vikram B, Chu FCH. Radiation therapy for metastases to the base of the skull. Radiology 1979;130:465–8. 69. Weber W, Rösler HP, Doll G, et al. Radiation therapy of osteolytic bone metastases. Onkol 1992;168:275–80. 70. Wilkins MF, Keen CW. Hemi-body radiotherapy in the management of metastatic carcinoma. Clin Radiol 1987;38:267– 8. 71. Williams CJ. Evidence-based cancer care. J Clin Oncol 1998;10:144–9. 72. World Health Organization. Cancer pain relief and palliative care. Report of a WHO expert committee. Tech Rep Ser: 804. Geneva: World Health Organization, 1990.

33

Rico K.Y. LIU, Raymond S.K. LO

Palliative Care for Patients with Advanced Cancer

Introduction

INTRODUCTION CHANGING THE MINDSET OF PHYSICIANS LIFE TRAJECTORY OF PATIENTS WITH INCURABLE CANCER MODEL OF AN INTEGRATED PALLIATIVE CARE SERVICE PRINCIPLES OF SYMPTOM CONTROL MANAGEMENT OF PREVALENT SYMPTOMS IN THE PALLIATIVE CARE SETTING CONCLUSION REFERENCES

Cancer is a common disease and is one of the most important causes of death worldwide. The Global Cancer Statistics published in 2002, reported that there were 10.9 million new cases of cancer, 6.7 million cancer deaths and 24.6 million persons alive with cancer [14]. In Hong Kong, cancer ranks first as the most common cause of death. In the year 2004, there were a total of 22,523 new diagnoses and 11,791 cancer deaths, which accounted for nearly one-third of all deaths in the territory [8]. On the whole, when patients are diagnosed as having advanced cancer, the disease is incurable; they live with the disease until the final days of life. In this journey, there can be a lot of uncertainties to face, difficult decisions to make, extreme emotions to encounter and physical symptoms to endure. Palliative care plays a vital role in helping patients through this phase of life by providing better symptom control, psychosocial care and, last but not least, facilitating acceptance of inevitable death. The World Health Organization (WHO) defined palliative care as: “The active total care of patients whose disease is not responsive to curative treatment. Control of pain, of other symptoms, and of psychological, social and spiritual problems is paramount. The goal of palliative care is achievement of the best quality of life for patients and their families” [22]. Although pain is the most important symptom requiring special management in cancer patients, other physical symptoms and psychological effects are equally distressful. Most advanced cancer patients suffer on average from 3.5 to six symptoms [5, 7]. Analysis of prevalence of discomforts other than pain showed that several symptoms are common in cancer patients, especially towards the terminal stage (Table 33.01) [2, 3, 4, 5, 6, 7].

538 Rico K.Y. LIU, Raymond S.K. LO

Table 33.01 Common symptoms other than pain causing distress in cancer patients [18] • Constipation • General weakness, apathy, cachexia, immobility and pressure sores • Anorexia • Nausea, emesis • Dyspnoea • Cough, hiccup • Dry mouth • Incontinence due to various causes • Open ulcers and their related consequences: foul smelling, discharge and bleeding • Disabilities related to malignant infiltration: paraplegia, bowel obstruction, ascites • Psychological distress, depression, anxiety, insomnia • Familial, social and economical distress.

The provision of palliative care has undergone major changes in recent years. In addition to the establishment of a Palliative Medicine subspecialty in the College of Physicians and the College of Radiologists, a growing number of trained oncologists are also equipped with the skills to deliver quality palliative care. Oncologists with palliative medicine training play a dual role in combining palliative care with oncological care. In this setting, palliative care is introduced early in the course of advanced disease while patients are still receiving treatment from oncologists, be it palliative chemotherapy or radiotherapy. This approach forms a major shift from mainly an endstage care stay in hospices in the past. Advanced cancer is not a homogenous condition. Patients may live from days to even years after diagnosis and the course of illness of each individual is unique. A palliative care specialist may encounter a multitude of situations as the disease progresses, which include physical needs, psychosocial needs, family related needs and spiritual needs. An interdisciplinary team involving doctors, nurses, counsellors and allied health professionals is essential to cater for these needs. Furthermore, an integrated care system, including in-patient care, day centre, home care, palliative care clinic and phone support, is important in delivering comprehensive services. In order to provide effective palliative care, it is necessary to integrate good symptom control, good communication skills and a thorough understanding

of the life trajectory of patients with advanced cancer. This chapter will outline elements involved in changing the mindset of doctors in caring for the advanced cancer patient, the life trajectory of advanced cancer patients, ways to integrate various components of the palliative care services and techniques in symptom control. The management of cancer pain is described in Chapter 9.

Changing the Mindset of Physicians The goals of palliative care are well set out in the definition of the WHO [21] and the patient’s comfort and quality of life are the main concerns. The decision to pursue a diagnosis will need to be balanced between the discomfort of related procedures and the benefit of treatment. This decision should be made on an individual basis and is associated with much clinical experience and judgement. The patient’s clinical state, life trajectory, knowledge of effects and toxicities of cancer treatment, and the patient’s and family’s wishes are all important aspects in the assessment. In general, there is more inclination to investigate and offer treatment if the patient’s physical condition is good. In the face of progressive disease and poor performance status, it may be appropriate to consider symptomatic care only, without the need to investigate all the causes of deterioration after balancing comfort care to benefit of specific treatment if a diagnosis is made. This contrasts with the emphasis of traditional medical training, which is commonly slanted towards the biomedical model in which the ultimate goal is to make a diagnosis and offer treatment specific to that diagnosis, while any psychosocial consideration and the patient’s quality of life are given lower priority. Consequently, in order to provide the optimal care to patients with incurable cancer, a change in the mindset of treating doctors is required to facilitate multidimensional management.

Life Trajectory of Patients with Incurable Cancer Caring for patients with incurable cancer requires a lot more than just attention to physical aspects

Palliative Care for Patients with Advanced Cancer 539

and good symptom control. Addressing the issue of uncertainty is very important in guiding these patients through the remaining course of their life. There may be many reasons for anxiety and worry when faced with what is going to happen in the future. It is common to hear the description from cancer patients that life is like a “time bomb”, not knowing when it will be set off. It may seem that life is so unpredictable as to make planning difficult. Another reason is the fear of death, the ultimate uncertainty in life. Contrary to the usual belief, the life trajectory of this group of patients follows a rather predictable course. Lunney described a pattern of functional decline in patients who died of cancer [11]. His report clearly demonstrated that the activity of daily living was well preserved until a median of 3 months before death. A small study carried out by a palliative care service in Hong Kong following a group of incurable cancer patients over 17 months showed similar results (Liu RKY, personal communication). In this study, 71 patients were followed and information on their performance status using the Eastern Cooperative Oncology Group (ECOG) Performance Status Grading [13] (body weight, unscheduled attendance, death) was recorded. There were 39 deaths and all except three of these patients progressed from ECOG I/ II to III, then IV before reaching the dying phase in a predictable manner. Three patients (8% of the deceased) progressed rapidly from ECOG I/ II to death over days and were considered to have unanticipated death. Schematic representation of the results is shown in Fig. 33.01. Results of this study indicated that the majority of patients with

Figure 33.01 The gradual decline in performance status with time until death.

incurable cancer maintain their performance status before reaching the dying phase and the chance of an unanticipated death is less than 10%. Problems and difficulties encountered by patients vary significantly depending on their performance status. Although they tend to have relatively fewer symptoms while their performance status is preserved, psychologically, they may face a great struggle coming to terms with the idea of living with an incurable disease. With the advance in cancer management, more options are now available, but they often come with a higher cost in treatment. It is becoming more difficult for patients and their families to balance benefit in continuing therapy which has a low chance of disease control against conservative management. Palliative care specialists with oncology training can greatly enhance care in this setting. They can present a clearer picture of information, balancing the chance of therapeutic success, the related toxicities and the goal of improving quality of life for the patient. The traditional beliefs of some ethnic groups require special attention in palliative care. For a Chinese patient, the promotion of a balanced diet is often important as most Chinese believe that certain foods can “stimulate” cancer growth. This misconception leads them to adopt a restricted diet low in animal protein. While a cure is not possible in cancer patients on palliative care, the goals of care are shifted towards enhancing the quality of life, having a positive attitude towards living with an incurable disease and to enjoying life. When performance status becomes compromised, more symptoms appear. The physical aspect of care with good symptom control is very important, but psychological care should not be ignored. It is not uncommon for patients with cancer to start thinking about their death. Various emotional reactions may surface as described by Kubler-Ross and these will require understanding and acceptance to facilitate adjustment [10]. Patients may have questions about the meaning of life and start talking about their own end-of-life planning. Being sensitive and the appropriate use of empathic reflections often help. Education and greater involvement of family members enhance the overall support to patients while going through this phase of continuing deterioration until it ends in the terminal stages. A schematic representation of the various needs over time is shown in Fig. 33.02.

540 Rico K.Y. LIU, Raymond S.K. LO

When the condition of patients further deteriorates such that they can no longer stay home, they are admitted to an in-patient hospice. As well as caring for the dying, the in-patient unit can provide patients with symptom control or respite care. A counselling service and particularly a bereavement service are important. In cases where a high risk of intense bereavement is identified, a more intensive service should be offered to the family well before the death of the patient. How different components of palliative care services can be integrated together in relation to the needs of patients is shown in Fig. 33.02. Figure 33.02 Schematic representation of various needs of the palliative care patient over time.

In order to deliver quality care, in addition to attention to symptom control, good communication skills and input from a multidisciplinary team are essential.

Model of an Integrated Palliative Care Service Modern palliative care services emphasise an early introduction of care for patients with incurable disease. Patients’ needs vary as they progress through the course of their illness, as described above. An integrated service needs to be multidisciplinary in nature and to incorporate the following components: out-patient clinic, day centre, palliative home care service and in-patient hospice service. Understanding the life trajectory and different needs of individual patients according to their performance status helps to tailor the palliative care service to those needs. When patients’ physical condition is good, they are cared for in an outpatient setting where great emphasis is placed on enhancing quality of life and living with the incurable disease. Functional rehabilitation should not be forgotten, as this may still be suitable in some circumstances with the goal of improving quality of life. When performance status deteriorates, patients and their families are assisted to understand what lies ahead. It is commonly a path of continual deterioration. Palliative home care service can be introduced and this will increase coping, with the aim of keeping patients at home as long as possible.

Principles of Symptom Control Symptom control in palliative care patients is truly an art as well as a science. Listed below are the five principles which serve as a useful practical guide to symptom control.

Subjectivity and multidimensionality of symptoms As with pain, it should be borne in mind that other disease symptoms are also subjective sensations with multidimensional components. The total pain concept as first proposed by Dame Cecily Saunders equally applies to all other possible symptoms in palliative care [17]. A physical distress inevitably has psychospiritual consequences, which can in turn aggravate the symptom sensation. Conversely, a psychological condition can present with or lead to physical problems. As an example, two common prevalent symptoms are dyspnoea and fatigue [18]. Dyspnoea is a frightening experience and can create a vicious cycle undermining the management and coping of the next symptom episode. It is not uncommon to encounter patients who have perfect oxygen saturation, yet continue to rely on oxygen. Similarly with fatigue, the physical component may be mild, yet it can be the psychospiritual factors such as depression and demoralisation which can affect the patient’s motivation and worsen the overall burden of fatigue. It cannot be overemphasised that the successful management of a symptom necessitates a

Palliative Care for Patients with Advanced Cancer 541

comprehensive and full interdisciplinary approach. In any setting, various non-medical dimensions can easily affect symptom perception in the cancer patient. Such factors can range from financial concerns, placement issues, self-esteem, dignity and burden, whether real or perceived. These issues are important considerations, though beyond the remit of this chapter.

Co-morbidity with multiple symptoms With the population ageing and the increasing chronic nature both of cancer and non-cancer palliative care conditions, the symptoms profile becomes more complicated with multiplicity and various interactions. In managing palliative care patients, it is essential not to over-focus on just the common symptoms (e.g. pain, dyspnoea) and neglect the others. Insomnia is an equally important and prevalent symptom, and adequate treatment can lead to overall better symptom control and quality of life [9]. Cough is yet another symptom which should be adequately palliated. It is advisable that routine screening of all symptoms should be conducted regularly in palliative care units. Not all distressing symptoms are obvious and easily recognised. Anorexia from cancer, cachexia or organ failure can sometimes be alleviated with simple measures such as dietary adjustment. Nausea is equally distressing, although it may not be obvious in the absence of coexisting vomiting. Palliative care patients are often affected by more than one coexisting illness [19]. Multiple medications become inevitable, with potential adverse effects rendering drug treatment and compliance more difficult [15]. Care should be exercised when prescribing medications to consider any interactions and side effects. This is especially so for older patients who are vulnerable due to limited physiological reserves. As with older patients, the presentation of palliative care patients’ symptoms can be atypical or nonspecific. Palliative care patients are often on steroids and may not be able to mount a fever response or may react with confusion when their condition deteriorates.

Prompt identification and relief of symptoms Prompt physical symptom control is a top priority in all palliative care patients. As mentioned, a comprehensive screening on admission will be helpful. An admission protocol serves this purpose well. In fact, it is of paramount importance that there should be periodic ongoing screening of symptom, such as performing a symptom checklist regularly two to three times per week. Standards should also be set, so that the aim of prompt control can be achieved, e.g. within 24 to 48 hours of admission. At the terminal phase, prompt treatment of symptoms such as death rattle, restlessness and delirium are especially urgent. A care pathway for the last 48 hours, if well designed, is a good tool to remind health care professionals to be alert and to provide rapid response for urgent symptom control. Symptom control should always be active rather than passive.

Identify potential treatable causes rather than give blanket treatment Notwithstanding the incurable nature of the disease from which palliative care patients suffer, many of their symptoms can have treatable causes. The cancer may not be curable, but the pain resulting from the cancer can be treated (see Chapter 9). Pain from cancer can result from many different causes, and treatment correspondingly varies. Similarly, dyspnoea in the palliative care setting may result from many different but treatable aetiologies, ranging from cancer to non-cancer causes [1]. Vomiting is not always due to intestinal obstruction and can result from other mechanisms. The choice of laxative should depend on the type of constipation, rather than being a blanket treatment. Despite this, however, it should not be misconstrued that all attempts at investigation must be conducted until an underlying cause is found. Careful consideration must be given to the risk and burden of each diagnostic test and treatment. The net result of each investigation and treatment should always bring the greatest benefit in the palliative care setting — and with minimal harm and discomfort.

542 Rico K.Y. LIU, Raymond S.K. LO

Ethical principles and quality of life Apart from the important ethical principles of beneficence, non-maleficence and futility as mentioned above, patient autonomy has to be respected above all. The patient has the right to refuse any interventions in the process of symptom control and treatment, provided that the patient is cognitively sound, adequately informed and not under any influence of mood or depressive conditions. In the Chinese setting, family consensus is pertinent and should also be taken into account, although strictly speaking the patient’s autonomy is the overriding factor. In assisting the patient to make rational choices, partnership rather than paternalistic decision-making should be adopted. Circumstances may arise where the patients’ decisions may not be in the professionals’ views the best clinical decisions. A dysphagic patient may refuse to have a nasogastric tube inserted as advised by the team. A patient with brain metastases may choose to forgo whole brain radiotherapy. An end-stage patient may not opt for any surgery or invasive endoscopy, even though the pathology can be salvageable. It is indeed the quality rather than the quantity of life which is the prime concern. The best interests here rest with the patient, not the professionals.

Management of Prevalent Symptoms in the Palliative Care Setting The treatment of cancer pain is discussed in Chapter 9 of this book. The causes and treatment of other prevalent palliative care symptoms are discussed in this section.

Dyspnoea As mentioned above, the non-pharmacological measures to alleviate the symptom of dyspnoea are also important, regardless of cause and aetiology, and should not be neglected.

Cough Cough is yet another frequent respiratory symptom in palliative care. Although it may not seem as

Table 33.02

Causes and treatment of dyspnoea in palliative care patients

Causes

Treatment [12]

Lung metastases

Steroids

Lymphangitis carcinomatosis

Steroids +/- diuretics

Superior vena cava obstruction

Steroids + urgent radiotherapy +/anticoagulation if any thrombosis

Malignant pleural effusion

Tapping/drainage if clinically indicated

Malignant pericardial effusion

Tapping/drainage if clinically indicated

Major airways obstruction/collapse

Steroids/radiotherapy/ stenting

Pre-existing heart failure or COAD

Diuretics or bronchodilators

Anaemia

Transfusion if symptomatic

Pneumonia

Antibiotics if symptomatic

Pulmonary emboli

Anticoagulation with heparin

Pneumothorax

Aspiration or chest drain if clinically indicated

Anxiety/panic attack/ hyperventilation

Reassurance/diversional therapy/anxiolytics

serious as dyspnoea, it can be equally distressing if refractory or being neglected. Like dyspnoea, cough again can have widely different causes, for which the treatment can be entirely different. A list of common causes in the palliative care setting is listed in Table 33.03. Symptomatic treatment of cough includes use of antitussives and mucolytics. For dry cough, antitussives alone can help. For productive cough with sputum, mucolytics may assist sputum expectoration and relieve the symptom. Commonly used antitussives include simple linctus, codeine phosphate and, in refractory cases, low dose opioids such as morphine or methadone, e.g. methadone 2.5–5 mg at night [12].

Palliative Care for Patients with Advanced Cancer 543

Table 33.03 Causes and treatment of cough in palliative care patients [12] Respiratory infection

Antibiotics

Aspiration of saliva

Suction; hyoscine butylbromide

Postnasal drip

Try antihistamines

Bronchospasm

Try bronchodilators

Oesophageal reflux

Try prokinetic drugs, e.g. maxolon, domperidone, and treat any oesophagitis accordingly

Heart failure

Diuretics

Drug induced, e.g. angiotensin converting enzyme inhibitor

Stop the causative drug

Malignant obstruction of airways

Radiotherapy/ chemotherapy/steroids

Death rattle The term refers to the sound made by excessive respiratory secretions in the throat which the dying patient is no longer able to clear. It may or may not be actually distressing to the patient, especially if the patient is not conscious, although it can be very disturbing to the relatives. Gentle suction if tolerated may suffice. The use of subcutaneous drugs such as hyoscine butylbromide or hyoscine hydrobromide delivered through a syringe driver is most effective [20].

Cachexia and anorexia Cachexia and anorexia are prevalent not just in cancer diseases but also in non-cancer related terminal conditions, such as end stage heart failure, or end stage respiratory disease. Treatment is often unsatisfactory and more research on the underlying pathophysiology is needed. Prokinetic agents are often used for cancer-associated dyspepsia. A trial of corticosteroids such as dexamethasone 4 mg daily or twice per day may help to stimulate the appetite and food intake, although the effect is short lived and prolonged use for more than 2 to 4 weeks is not generally recommended. Progestational agents such as megestrol acetate have been used with some success, although side effects like oedema,

thrombosis and hypertension may limit their use. Synergistic use of progestational agents and nonsteroidal anti-inflammatory drugs such as ibuprofen have also been shown to be effective, if there is no contraindication. Omega-3 fatty acids have also been tried, although large doses are needed. Diet preference, eating habits, the environment for meals and the pleasure of company are also important non-pharmacological factors.

Nausea and vomiting Nausea and vomiting are prevalent gastrointestinal symptoms in palliative care and they require a diagnostic approach. The pathophysiology of nausea and vomiting can be broadly divided into the following four mechanisms: psychological via the cortex; motion and position stimuli via the vestibular apparatus; drugs, carcinomatosis, uraemia and ketosis via the chemoreceptor trigger zone; and Table 33.04 Causes and treatment of nausea and vomiting in palliative care patients [12] Raised intracranial pressure

Steroids; treat underlying cause

Hypercalcaemia

Hydration; bisphosphonates

Uraemia

Hydration; haloperidol

Constipation

Relieve constipation with appropriate laxatives

Urinary tract infection

Antibiotics

Drug induced

Stop the contributing drugs

Opioid induced

Try maxolon, stemetil, or haloperidol (symptoms often subside after few days)

Gastric stasis

Prokinetic agents, e.g. metoclopramide or domperidone

Gastritis

Stop offending drugs; antacids

Peptic ulcers

H2 antagonists, proton pump inhibitors

Squashed stomach syndrome

Dietary adjustment; prokinetic agents

544 Rico K.Y. LIU, Raymond S.K. LO

gastric irritation/distension or gut efferents via the abdominal organs. The final pathway is through the vomiting centre. The management of common causes of vomiting in the palliative care setting is described in Table 33.04. Squashed stomach syndrome is particularly common when a large liver tumour or metastases or other intra-abdominal masses compress the stomach, giving rise to early satiety and vomiting, and sometimes heartburn and hiccup. Dietary adjustment with smaller meals of softer consistency at more frequent intervals may be helpful, in addition to prokinetic drugs.

Malignant intestinal obstruction Obstruction is probably the most feared gastrointestinal symptom in the palliative care setting, although it often can be successfully managed [16]. The conventional drip and suck approach can often be alleviated with appropriate subcutaneous infusion of drugs, avoiding the added discomfort of a nasogastric tube. A cocktail of drugs usually consists of the following: • •

Constipation

•

Even a seemingly trivial symptom such as constipation can have a devastating impact on the patient’s comfort and quality of life. Constipation may be complicated with anorexia, vomiting, urine retention, spurious diarrhoea, faecal incontinence and even intestinal obstruction. Like any other symptom, the management of constipation also requires a diagnostic approach. Secondary causes such as depression, hypercalcaemia, or side effects from drugs should be identified. Treatment of hard constipation requires softeners or osmotic laxatives rather than stimulants. Manual evacuation is often the first step needed for severe faecal impaction. Soft faeces can also lead to constipation, especially in patients with weak abdominal or pelvic muscles such as in cord or cauda equina compression; in severely dyspnoeic patients who are too breathless to defaecate; or in weak and frail bed-bound patients who are lying supine. Soft constipation requires stimulant laxatives rather than further softeners.

•

Opioids invariably lead to constipation if the symptom is inadequately prevented or treated. Constipation should always be cleared before commencement of opioids; and laxatives should always be prescribed together with opioids. It may be safer to err on the side of loose stools rather than waiting for constipation to occur, for by then compliance in continuing opioid treatment may be undermined. Laxatives should be proportionally increased with increase of opioid doses. Adequate fluid intake helps, but an increase of dietary fibre may not be well tolerated in the terminal setting.

•

Haloperidol or cyclizine or both to control the vomiting Buscopan to relieve the colic and also reduce the intestinal secretions Opioids if necessary to relieve severe abdominal or other cancer pain Steroids with trial use of dexamethasone to reduce tumour mass and relieve obstruction Prokinetic agents such as metoclopramide may be tried if obstruction is not complete and the patient is free of colic.

Second-line treatment can include subcutaneous injection or infusion of octreotide. Surgical interventions such as venting gastrostomy or stenting can be considered if appropriate. For high level intestinal or gastric obstruction, decompression with a nasogastric tube is sometimes warranted. Faecal impaction should always be considered and removed by softeners and enemas. Care should be taken to differentiate obstruction from ileus, which requires different treatment with prokinetics agents and attention to any underlying metabolic or electrolyte disturbance.

Anxiety, restlessness and depression In facing adversities and life-threatening illnesses, anxiety, restlessness and depression may be prevalent although not always inevitable. With adequate support and counselling, positive coping strategies can be facilitated, and psychological distress does not always necessitate drug treatment. Attention to social and spiritual issues is part of the comprehensive spectrum of holistic palliative care and should not be neglected. For severe or refractory psychological symptoms, drug treatment may be indicated. Benzodiazepines may be used, e.g. lorazepam or diazepam. Caution must be exercised in the elderly in using benzodiazepines,

Palliative Care for Patients with Advanced Cancer 545

as they may cause confusion. Oral or subcutaneous midazolam may be tried in severe restlessness and agitation, especially in the terminal phase. For insomnia, benzodiazepines, or non-benzodiazepines like zopiclone or zolpidem can be tried because of their lower incidence of side effects. Depression requires conventional drug treatment with tricyclic antidepressants or selective serotonin reuptake inhibitors, although the time needed for onset of action should be taken into account for terminal cases.

Table 33.05 Causes and treatment of oedema in palliative care patients [12] Dependent oedema

Elevation; stocking; exercise

Drug induced, e.g. calcium antagonists

Avoid causative drug

Fluid retention

Adjust fluid intake

Hypoalbuminaemia

Increase protein intake

Heart failure

Diuretics + other conventional treatment

Cor pulmonale

Diuretics + other conventional treatment

Cirrhosis

Diuretics + other conventional treatment + ascitic tapping if indicated

Renal failure

Diuretics + other conventional treatment

Deep vein thrombosis

Anticoagulants if no contraindication

Superior venous cava obstruction

Urgent radiotherapy + steroids

Lymphoedema

Specific treatment with massage, bandaging, lymphopress as appropriate

Confusion and delirium The first important step in management is in confirming whether there is true confusion. Frequently for the older person, confusion at night is just the sun-downing effect due to the deprivation of sensory stimulation. An adequate explanation given to patients and relatives, together with a calm environment help provide reassurance. Secondary causes such as hypoxia, sepsis, drug side effects and electrolyte disturbances need to be identified as they are eminently treatable. Delirium may aggravate symptoms in pre-existing dementia, and treatable causes should be identified. In patients with agitation or delirium associated with hallucinations and paranoia, oral or subcutaneous haloperidol is the first-line treatment. Second-line atypical antipsychotics, e.g. risperidone, can be used if haloperidol is not preferred. Midazolam or chlorpromazine can be added for further sedation if needed.

Oedema Oedema is often present in palliative care patients and again can have protean causes. It is imperative first to identify whether the oedema is affecting the patient’s quality of life. If not, mild symptoms may not need to be treated. Simple causes of oedema such as dependent oedema can be treated with non-drug measures. Common causes of oedema are listed in Table 33.05. Fluid restriction is usually not applicable in palliative care patients who already have low diet and fluid intake. A low salt diet is not palatable and impairs quality of life in the final stages. Diuretics are often needed in severe conditions, and the intravenous route may be required if there is significant gut oedema impairing absorption. Worsening renal impairment may be a concern,

although at the end of life adequate symptom relief may be a more important and overriding factor. A trial of synergistic use of diuretics with intravenous albumen may be helpful with refractory oedema in hypoalbuminaemic states. Percutaneous drainage of fluid with a cannula in oedematous limbs has also been successfully tried with good response.

Conclusion Palliative care for the advanced cancer patient necessitates prompt and effective symptom control, using a diagnostic rather than a blanket approach. It should aim to deliver maximum benefit with minimal burden or harm. Attention needs to be given to coexisting symptoms from non-cancer as well as cancer conditions. The ultimate aim of symptom control in the palliative care setting is to improve quality of life.

546 Rico K.Y. LIU, Raymond S.K. LO

References 1.

2.

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22.

Chan KS, Sham MM, Tse DM, et al. Palliative medicine in malignant respiratory diseases. In Doyle D, Hanks G, Cherny N, Calman K, eds. Oxford Textbook of Palliative Medicine, 3rd edn. Oxford: Oxford University Press, 2004:587– 618. Cherny N, Sapir R, Catane R, et al. Symptom prevalence and severity among ambulatory patients attending an integrated oncology-palliative care day hospital. Proceedings of the Annual Meeting of the American Society of Clinical Oncology. 1999;18:A2247. Coyle N, Adelhardt J, Foley KM, et al. Character of terminal illness in the advanced cancer patient: Pain and other symptoms during the last four weeks of life. J Pain Symptom Manage 1990;5(2):83–93. Cummings-Ajemian I. Treatment of related symptoms. In Patt RB, ed. Cancer Pain. Philadelphia: Lippincott Raven, 1993:197–208. Curtis EB, Krech R, Walsh TD. Common symptoms in patients with advanced cancer. J Palliat Care 1991;7:25–9. Donnelly S, Walsh D. The symptoms of advanced cancer. Semin Oncol 1995;22:67–72. Grond S, Zech D, Diefenbach C, et al. Prevalence and pattern of symptoms in patients with cancer pain: A prospective evaluation of 1,635 cancer patients referred to a pain clinic. J Pain Symptom Manage 1994;9:372–82. Hong Kong Cancer Registry, Hospital Authority. Available at http://www3.ha.org.hk/cancereg/data/all.pdf. Hugel H, Ellershaw JE, Cook L, et al The prevalence, key causes and management of insomnia in palliative care patients. J Pain Symptom Manage 2004;27(4):316–21. Kubler-Ross E. On Death and Dying: What the Dying Have to Teach Doctors, Nurses, Clergy, and Their Own Families. New York: Touchstone, 1997. Lunney JR, Lynn J, Foley DJ, et al. Patterns of functional decline at the end of life. JAMA. 2003;14;289(18):2387– 92. Lo RSK, ed. New Territories East Handbook on Symptom Control, 2nd edn. Shatin Hospital and Bradbury Hospice, Hospice and Palliative Care Services, 2007. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–55. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics. CA Cancer J Clin 2005;55:74–108. Riechelmann RP, Zimmermann C, Chin SN, et al. Potential drug interactions in cancer patients receiving supportive care exclusively. J Pain Symptom Manage 2008;35(5):535–43. Ripamonti C, Fagnoni E, Magni A. Management of symptoms due to inoperable bowel obstruction. Tumori 2005;91(3):233–6. Saunders C. The Management of Terminal Illness. London: Edward Arnold, 1967. Tsui SL. Cancer pain. In Yang JCS, Tsui SL, eds. A Guide to Pain Medicine. Hong Kong: Hong Kong University Press, 2002:234. Wedding U, Roehrig B, Klippstein A, et al. Comorbidity in patients with cancer: Prevalence and severity measured by cumulative illness rating scale. Crit Rev Oncol Hematol 2007;61(3):269–76. Wildiers H, Menten J. Death rattle: Prevalence, prevention and treatment. J Pain Symptom Manage 2002;23(4):310– 7. WHO definition of palliative care. Available at http://www.who.int/cancer/palliative/definition/en. WHO guidelines. Cancer Pain Relief, 2nd edn. Geneva: World Health Organization, 1996.

34

Anne KWAN

Acupuncture and Traditional Chinese Medicine

INTRODUCTION HISTORY OF ACUPUNCTURE TYPES OF ACUPUNCTURE PRACTICE EFFECTS OF ACUPUNCTURE ACUPUNCTURE NOMENCLATURE ACUPUNCTURE TECHNIQUE ACUPUNCTURE FOR SOME PAIN CONDITIONS Acupuncture for recurrent headaches Acupuncture for dental pain Acupuncture for facial pain Acupuncture for shoulder pain Acupuncture for osteoarthritis Acupuncture for low back pain Acupuncture for other symptom relief OTHER FORMS OF ACUPUNCTURE SAFETY OF ACUPUNCTURE CONCLUSION REFERENCES

Introduction There are numerous established medical treatments for chronic pain. Most of the conventional treatments have been well studied and the effectiveness of these treatments is supported by positive evidence. Complementary and alternative medicine on the other hand is still lacking in convincing evidence to prove that it is effective. Despite that, for various reasons, it enjoys high popularity and is employed at increasing frequency. Due to the diverse spectrum and mystical nature of complementary and alternative medicine, sound scientific studies are difficult to conduct. Although acupuncture is one of the better studied of its modalities, strong evidence supporting its use is still lacking. Numerous text books and manuals have already been written on the use of acupuncture for pain, so it is unrealistic and not useful to have a comprehensive review of the subject as part of this textbook. This chapter is, therefore, simply intended to give a general overview of acupuncture in chronic pain management.

History of Acupuncture Acupuncture has been used in China for over 3,000 years. Needles were made from stones before the discovery of metals. A stone needle unearthed in Toudaowa, Dolun Banner, in Inner Mongolia in 1963 is thought to date from the Neolithic Age (about 4 to 10 thousand years ago). Stone needles were replaced gradually by bone and bamboo needles until metal casting techniques were invented. All sorts of metals have been used. Bronze needles were the oldest type and needles made of the precious metals gold and silver have also been used. Today, most needles are made from stainless steel. Single-use disposable needles are the most popular type, as sterilisation is a major concern with re-used needles. Around the 12th

548 Anne KWAN

century, with increasing sea-travel and widespread global trading, the technique of acupuncture spread from China to other Asian countries such as Japan, Korean, Vietnam and India. While the westward spread of acupuncture started in the 19th century, acupuncture development in China went through a period of rejection around the middle of the

Table 34.01

Qing dynasty. However, interest in acupuncture returned in the early 1950s after the establishment of the People’s Republic of China [3]. In fact, acupuncture on its own or as part of Traditional Chinese Medicine (TCM) enjoyed tremendous popularity in Western countries from the 1970s after President Nixon visited China. Today, active

Diseases which can be treated with acupuncture as suggested by the WHO

Body part

Conditions

Upper respiratory tract

Acute sinusitis Acute rhinitis Common cold Acute tonsillitis

Respiratory system

Acute bronchitis Bronchial asthma

Disorders of the eye

Acute conjunctivitis Central retinitis Myopia (in children) Cataract (without complications)

Disorders of the mouth

Toothache, post-extraction pain Gingivitis Acute and chronic pharyngitis

Gastrointestinal disorders

Spasm of oesophagus and cardia Hiccup Gastroptosis Acute and chronic gastritis Gastric hyperacidity Chronic duodenal ulcer (pain relief) Acute duodenal ulcer (without complications) Acute and chronic colitis Acute bacillary dysentery Constipation Diarrhoea Paralytic ileus

Neurological and musculoskeletal disorders

Headache and migraine Trigeminal neuralgia Facial palsy (early stage) Pareses following a stroke Peripheral neuropathies Sequelae of poliomyelitis (early stage,) Ménière’s disease Neurogenic bladder dysfunction Nocturnal enuresis Intercostal neuralgia Cervicobrachial syndrome Frozen shoulder Tennis elbow Sciatica Low back pain Osteoarthritis

Acupuncture and Traditional Chinese Medicine 549

societies and associations of acupuncture can be found in most Western countries. Courses and workshops in acupuncture are regularly conducted all over the world to teach medical practitioners and physiotherapists its theory and techniques. In 1979, the World Health Organization (WHO) recognised the value of acupuncture in the treatment of 43 clinical conditions (Table 34.01) [29]. A number of these approved conditions are frequently encountered in pain clinics.

Types of Acupuncture Practice Although acupuncture is basically a technique which involves needling of skin and underlying tissues, the position, depth and stimulation technique of the needles vary among different schools. Based on the relative dominance of the technique in traditional concepts and biomedical models, Birch et al. categorised acupuncture practice into five levels (Table 34.02) [2]. Table 34.02

Birch, Felt and Lytle’s classification

1. Adherence to traditional concepts only, with complete rejection of biomedical model. 2. Adherence to traditional concepts, with limited utilisation of biomedical model. 3. An interweaving and mixing of traditional and biomedical concepts. 4. Adherence to biomedical concepts, with the subsuming of traditional concepts where they can be subsumed. 5. Adherence to only biomedical concepts, with complete rejection of traditional concepts.

In view of the different theoretical concepts, technical approaches and treatment targets, Kenner in 1994 proposed classifying acupuncture into four main types of practice (Table 34.02) [10]. It is important to understand the different types of acupuncture practice. Most of the recent clinical studies used one of the first two types of acupuncture practice described by Kenner, or a combination of both. In contrast, all TCM practitioners use channel acupuncture. Atypical acupuncture of microsystems is being used increasingly for health regulatory

Table 34.02

Kenner’s classification of types of acupuncture practice

1. Acupuncture analgesia (including the intensive stimulation method intended for pain control). 2. Acupuncture physical therapy (the needling of anatomical structures such as trigger and motor points). 3. Channel acupuncture (including most traditional methods). 4. Homuncular acupuncture (microsystems such as scalp, ear, hand, foot or nose acupuncture).

reasons. The efficacy of these practices is still unclear and awaits support by scientific evidence. Unless the acupuncture technique used in the clinical trials is standardised and the acupoints are well defined, it is difficult to obtain consistent or positive results even with sound research methodology and adequate sample size. When comparing efficacy, it is more logical to have the treatment group compared with a control group receiving sham acupuncture instead of no acupuncture. However, for most of the better-designed studies, the control group also received intensive needle stimulation in the sham acupoints, which could also result in pain relief from endogenous opioid release. The placebo effect also plays a significant role in pain relief, making comparative study without sham acupuncture hard to interpret.

Effects of Acupuncture At least two theories explaining the effects of acupuncture are supported by evidence. The gatecontrol theory hypothesises that the acupuncture needles stimulate A delta fibres entering the dorsal horn of the spinal cord. These in turn mediate segmental inhibition of pain impulses carried in the unmyelinated C fibres and, through connections in the midbrain, enhance descending inhibition of C fibre pain impulses at other levels of the spinal cord. The other theory suggests that acupuncture needling stimulates release of endogenous opioids and other neurotransmitters such as serotonin [25]. The increase in beta-endorphin level is not confined to blood alone. A study conducted in the 1980s found that patients with pain had increased beta-endorphin in the lumbar cerebrospinal fluid after electro-acupuncture [4]. Recent advances in medicine obviously provide more powerful

550 Anne KWAN

neuroimaging tools for the scientific study of acupuncture. Studies using positron emission tomography have shown that the thalamic asymmetry present among patients suffering from chronic pain was reduced after the patients underwent acupuncture treatment. Other studies using functional magnetic resonance imaging have pointed to a relationship between particular points and visual cortex activation [20]. Other effects of acupuncture are also widely studied. Some of these effects may help to explain the phenomenon of analgesia and recovery from chronic pain. In addition to an increase in betaendorphin level for more than 24 hours after acupuncture treatment, one study showed that the majority of patients also had an increase of CD3, CD4 and CD8 values 24 hours after stimulation. Half of the patients had increased monocyte phagocytosis 30 minutes after stimulation and all patients had increased activities 24 hours after stimulation [16]. Although the significance of these findings is unclear, the effect seems to do more good than harm. Generally, the effect of acupuncture takes hours to build up and days to wear off. The TCM theory based on the meridian principles explains the analgesic effect in terms of relieving the blocked “qi” along the meridians. Qi normally flows freely in a defined direction along the 12 regular and other extra meridians. Qi blockage can cause pain and other disease conditions. Regulating

the flow with needling and manipulation restores the flow and removes pain [22]. In order to achieve the maximum effect, treatment provided twice a week is usually recommended. Daily treatment may bring about quick relief initially, but it is generally not necessary. A treatment usually takes 20 to 30 minutes. A course of treatment consists of about 10 treatments. A full course of acupuncture can be repeated, but a few weeks should be allowed in between. The rest in between courses of treatment allows restoration of endorphin level. Painful conditions should not be treated solely by acupuncture as the patient may become dependent on the pain relief effect. Other modalities such as physiotherapy and psychological intervention, to include relaxation skills, pacing technique, biofeedback and cognitive behavioural therapy, should also be used as part of a multimodal approach to managing chronic pain.

Acupuncture Nomenclature Most of the acupoints are on the meridians; hence, it is possible to use two alphabet letters to indicate the meridians where the acupoints are found and a number after the letters to locate the exact site. Standardised nomenclature helps to communicate the exact acupoints being used. It also facilitates training of acupuncturists whose first language is not Chinese. Obviously, Chinese names are still frequently used in Chinese speaking countries.

Table 34.03 Standard acupuncture nomenclature proposed by the WHO LU (or L)

Lung meridian

TE

Triple energiser meridian

LI

Large intestine meridian

GB

Gall bladder meridian

ST

Stomach meridian

LR (or LIV)

Liver meridian

SP

Spleen meridian

GV

Governor vessel

HT (or H)

Heart meridian

CV

Conception vessel

SI

Small intestine meridian

EX-HN

Extra points — head and neck

BL (or B)

Bladder meridian

EX-B

Extra points — back

KI (or K)

Kidney meridian

EX-UE

Extra points — upper extremities

PC (or P)

Pericardium meridian

EX-LE

Extra points — lower extremities

Acupuncture and Traditional Chinese Medicine 551

Ashi points are points at which a patient feels intense pain and they are very similar to trigger points. Some of the alphabetical nomenclature for the meridians is shown in Table 34.03.

Acupuncture Technique Locating acupoints There are three ways of locating the acupoints. The most common method is by recognising surface landmarks. The second method is by proportion, which is used to find acupoints located between two landmarks. Some acupoints are at a short distance from a surface landmark and the distance is usually measured by “tsun” or “cun”. One tsun equals the width of the distal phalangeal joint of the patient’s thumb. The width of the patient’s palm is around three tsun. Apart from using anatomical means for location, acupoint locators using reduction in resistance or capacitance are also used with varying degrees of success. The choice of acupoints for each condition is controversial and the approach is still far from uniform. Some acupoints are better known for their effects on certain conditions, hence, they are used more frequently. As most acupuncturists use more than one acupoint, it is hard to suggest one point for a particular condition. Studies on efficacy of acupuncture usually compare a group of acupoints with sham points which are adjacent to the treatment acupoints. As the choice is so variable, it adds difficulty in the design of acupuncture research studies. Most acupuncturists use no more than 10 acupoints for the first few treatments. More acupoints can be added later on when patient gets used to the stimulation of needles and the unique sensation. Acupoints located close to the area of disease, e.g. head region for headache and back for back pain, are known as local points. Points located at a distance from the disease area are known as distance points. The idea of using distal acupoints is to regulate the qi. Some distance acupoints are well known for their effect. The ST 36 (Zusanli) acupoint is a well-known example for constipation, diarrhoea or stomach discomfort. The well-studied PC 6 (Neiguan) is a frequently used acupoint for treatment of nausea and vomiting. Unilateral local acupoints on the same side as the diseased area are

used. Bilateral or sometimes distance acupoints on the opposite side of the disease area are used because of their general effect. Based on the five-element theory and the theory of yin-yang, a collection of acupoints is used by traditional acupuncturists for a particular condition. As time and date are important parts of the yingyang theory, needling a collection of acupoints according to the time of injury and treatment is also practiced by some traditional acupuncturists. Traditional acupuncturists also apply moxibustion to some of the acupoints. This manoeuvre promotes flow of qi, which in turn enhances some of the therapeutic effect. An alternative to moxibustion is to apply infrared light to warm up the diseased area.

Needles Before attempting to insert the acupuncture needles, it is important to be familiar with the equipment and the exact locations of the acupoints. Most acupuncture needles used today are filiform needles comprising a handle and a body. Other acupuncture needles, such as the press needles or seven star needles, are still used by TCM practitioners for special conditions. The ordinary filiform needle is normally classified by length and diameter. Commonly, solid single-use needles 2 to 4 cm long and of diameter 0.25 to 0.3 mm are used. Very long needles penetrating two acupoints are used by traditional acupuncturists for pointto-point acupuncture. Laser and short waves are employed in some centres to replace traditional needles. The efficacy of these devices is still under investigation.

Needling technique Disposable sterile acupuncture needles are commonly used in modern practice, otherwise full sterilisation steps must be strictly employed. It is mandatory to employ an aseptic technique for needle insertion. Needle application can be aided by pressing the skin with a finger, pinching the skin, or tensing the skin by spreading it. Alternatively, a needle placed within a tube can help accurate and painless needle placement. The needle can be inserted perpendicularly downward or at a slanting angle. The depth of needle insertion is important to achieve the desired effect [8].Once the needle is place correctly, a tight grabbing effect

552 Anne KWAN

can be felt and it is not easy to pull the needle out unintentionally. Patients also complain of swelling, heaviness, numbness and soreness at the insertion site. Some acupoints are more sensitive than others. When LI 11 (Quchi) is stimulated, a sensation of warmth with a flow of current towards the shoulder or down the hand may be experienced. In order to obtain a good effect, most needles can be stimulated. The traditional acupuncturists can manipulate a needle by turning it clockwise or anticlockwise at very high frequency. The frequency, direction of turning and the force of moving the needle in or out are important in the traditional Chinese acupuncture technique as they determine whether qi along the meridian is enhanced or reduced. Electrical stimulation delivered by a battery-powered multi-channel nerve stimulator is employed in the modern day practice. Continuous stimulation at a frequency of 2 Hz is most frequently used. The intensity is adjusted for maximum stimulation while the patient still feels comfortable. The current is usually in the range of 20 to 30 mA. After a couple of treatments, once the patient gets used to the stimulation, the stimulating current can usually be turned up to achieve better effect. As it is undesirable to have Table 34.04

patients falling off the chair during treatment, patients should be placed in a well-supported and comfortable position. It is not uncommon to find patients falling asleep. Stimulation of needles for 20 minutes is commonly done. Although theoretically, the placement of the active and inactive electrodes may regulate the flow of qi, it is customary to place the active electrode over the acupoints which most need to be stimulated.

Acupuncture for Some Pain Conditions Acupuncture for recurrent headaches Acupuncture is sometimes used in the treatment of recurrent headaches. Acupoints which can be used for this condition are listed in Table 34.04. Short-term pain relief is frequently encountered. As most recurrent headaches can be effectively treated with medications, the use of acupuncture is recommended for the severe form or acute or chronic type of headaches only. Despite there being some strong proponents of this mode of therapy

Some acupuncture points for headache

Points

Location

Technique

BL 2 (Cuanzhu)

Medial end of eyebrow

Slanting needling of 0.3 tsun

BL3 (Meichong)

0.5 tsun above BL 2

Straight needling of 0.3 tsun

BL 4 (Quchai)

0.5 tsun above and 1.5 tsun lateral to middle of anterior hairline

Straight insertion of 0.5 tsun

BL 5 (Whuchu)

1 tsun above and 1.5 tsun lateral to middle of anterior hairline

Straight insertion of 0.5 tsun towards front side

BL 6 (Chengguang)

2.5 tsun above and 1.5 tsun lateral to middle of anterior hairline

Straight insertion of 0.5 tsun

BL7 (Tongtian)

4 tsun above and 1.5 tsun lateral to middle of anterior hairline

Straight insertion of 0.5 tsun

BL 9 (Yuzhen)

2.5 tsun above and 1.3 tsun lateral to middle of posterior hairline

Straight insertion of 0.5 tsun

BL 10 (Tianzhu)

0.5 tsun above and 1.3 tsun lateral to middle of posterior hairline

Straight insertion of 0.5 tsun

ST 8 (Touwei)

0.5 tsun above and 4.5 tsun lateral to anterior hairline

Straight insertion of 0.5 tsun

LI 4 (Hegu)

Midpoint of medial aspect of 2nd metacarpal

Straight insertion of 0.5 tsun

Acupuncture and Traditional Chinese Medicine 553

Table 34.05

Some acupuncture points for dental pain

Points

Location

Technique

ST 6 (Jiache)

0.5 tsun anterior and superior to angle of mandible

Straight insertion of 0.5 tsun towards front side

ST 7 (Xiaguan)

Depression below midpoint of zygoma

Straight insertion of 0.5 tsun

LI 4 (Hegu)

Midpoint of medial aspect of 2nd metacarpal

Straight insertion of 0.5 tsun

LI 10 (Shousanli)

2 tsun below LI 11

Straight insertion of 0.5 tsun

LI 11 (Quchi)

Midpoint between lateral epicondyle and lateral end of transverse crease at elbow

Straight insertion of 1 tsun

Acupuncture for dental pain

trials imply that acupuncture is effective in dental analgesia. As suggested by the authors, the important questions which remain unanswered are the optimal acupuncture techniques and acupuncture’s relative efficacy compared with conventional methods of analgesia [9]. Some of the commonly used acupoints for dental pain are shown in Table 34.05. Acupoint LI 4 (Hegu) is frequently recommended for acute toothache. Apart from needling, digital pressure onto the point on the same side as the toothache for 10 to 15 minutes can bring about effective analgesia.

Acupuncture is frequently advocated as an effective treatment for dental pain. To assess its effectiveness, a systematic review of 16 controlled studies was conducted. The findings of the majority of these

Literature searches performed by the Royal Society of Medicine and the University Library, Copenhagen were able to identify 74 publications regarding the use of acupuncture in dentistry.

among practitioners, evidence supporting its use is not fully convincing. A systematic review of 22 trials, which included a total of 1,042 patients, was conducted. Of the trials, 15 were conducted on migraine, six on tension headache and one trial had patients with various headaches. The majority of the 14 trials comparing true and sham acupuncture showed at least a trend in favour of true acupuncture. The eight trials comparing acupuncture and other treatment forms had contradictory results [14].

Table 34.06 Acupuncture points for facial pain or spasm Points

Location

Technique

LI 20 (Yingxiang)

0.5 tsun beside the ala nasi

Slanting needling of 0.3 tsun

ST 2 (Sibai)

Just over infraorbital foramen

Straight needling of 0.2 tsun deep towards S4

ST 4 (Dicang)

0.4 tsun beside angle of mouth

Straight insertion of 0.5 tsun deep towards S6

ST 6 (Jiache)

0.5 tsun anterior and superior to angle of mandible

Straight insertion of 0.5 tsun towards front side

ST 7 (Xiaguan)

Depression below midpoint of zygoma

Straight insertion of 0.5 tsun

S118 (Quanliao)

Lateral canthus line, lower border of zygomatic bone

Straight insertion of 0.5 tsun

BL2 (Cuanzhu)

Medial end of eyebrow

Straight insertion of 0.2 tsun

EX-HN 4 (Yuyao)

Middle of eyebrow

Slanting needling of 0.3 tsun

554 Anne KWAN

However, only six publications in the treatment of temporomandibular disorders (TMD) were randomised and blinded. The six publications involved only three studies and they all proved acupuncture effective for treatment of TMD. The local points recommended for treatment of TMD are ST 6, ST 7, SI 18, GV 20, GB 20, BL 10 and a distance point LI 4 [5].

Acupuncture for facial pain Acupuncture treatment for pain on the face has not been studied extensively, although use of this form of complementary therapy is rather common. A Swedish study with only 10 patients enrolled using four methods for evaluating the effect of treatment (subjective evaluation, clinical dysfunction index according to Helkimo, intensity of pain according to a visual analogue scale and medication consumption) showed encouraging results. The authors concluded that acupuncture may be a realistic alternative to other conventional treatment for some patients with long-lasting chronic facial pain [19]. Some of the acupoints used for either pain or spasm are shown in Table 34.06.

because of the pain and associated muscle spasm. Acupuncture may be used on its own for pain management as well as part of the physiotherapy. Acupoints around the neck commonly used to treat this condition are shown in Table 34.07. Distal points can be used to facilitate neck movement. Acupoint LU 7 (Lieque) is a well-known point for this purpose. Needling of LU 7 (Lieque) on the same side of the neck pain or stiffness for 20 minutes may bring about short-term relief. A study comparing the efficacy of acupuncture and conventional massage for treatment of chronic neck pain revealed that 1 week after five treatments the acupuncture group had a significantly greater improvement in motion-related pain compared with massage but not compared with sham laser. The acupuncture group had the best results in most secondary outcome measures (range of motion, pain related to movement in six directions, pressure pain threshold, changes of spontaneous pain, motionrelated pain, global complaints and quality of life [Short Form Health Survey: SF-36]). The authors concluded that acupuncture is an effective shortterm treatment for patients with chronic neck pain, but there is only limited evidence for long-term effects after five treatments [12].

Acupuncture for neck pain Chronic neck pain may be resistant to pharmacological and physical treatments. Patients may be reluctant to have intense physiotherapy Table 34.07

Acupuncture for shoulder pain Painful or frozen shoulder is usually treated with medications and mobilisation. Acupuncture is

Some acupoints for neck pain

Points

Location

Technique

S1 9 (Jianzhen)

1 tsun above posterior axillary fold

Straight insertion of 1–1.5 tsun deep

S1 12 (Pingfeng)

Middle of suprascapular fossa

Straight insertion of 1–1.5 tsun deep

BL 10 (Tianzhu)

Lateral margin of trapezius muscle, 0.5 tsun above occipital hairline

Straight insertion of 1–1.5 tsun deep

GB 20 (Fengchi)

Lateral margin of trapezius muscle, 1 tsun above occipital hairline

Straight insertion of 1–1.5 tsun deep

LI 11(Quchi)

Midpoint between lateral epicondyle and lateral end of transverse crease at elbow

Straight insertion of 1–1.5 tsun deep

GV14 (Dazhui)

Between 7th vertebra and the 1st thoracic vertebra

Slanting insertion of 1–1.5 tsun deep

GV16 (Fengfu)*

1 tsun above GV15, i.e. 1.5 tsun above occipital hairline, below occipital protuberance

Straight insertion of 1–1.5 tsun deep

* Acupoint adjacent to an important anatomical structure, caution is required.

Acupuncture and Traditional Chinese Medicine 555

Table 34.08

Some acupoints for shoulder pain or frozen shoulder

Points

Location

Technique

LI 11 (Quchi)

Midpoint between lateral epicondyle and lateral end of transverse crease at elbow

Straight insertion of 1–1.5 tsun deep

LI 14 (Binao)

7 tsun above LI 11 on a line joining LI 11 and LI 15

Straight insertion of 1 tsun deep

LI 15 (Jianyu)

Depression between acromion and anterior aspect of humoral head

Straight insertion of 0.5 tsun deep

TE 14 (Jianliao)

Depression at back of shoulder when arm is abducted

Straight insertion of 1 tsun deep

GB 21 (Jianjing)*

Midpoint between GV14 and acromion of scapular

Straight insertion of 0.5 tsun deep

SI 9 (Jianshen)

1 tsun above posterior axillary fold

Straight insertion of 1 tsun deep

SI 11 (Tianzong)

Centre of infraspinous fossa of scapula

Straight insertion of 0.5 tsun

* Acupoint adjacent to an important anatomical structure, caution is required.

being increasingly employed with the hope of reducing analgesic requirement and shortening the duration of treatment. A well-designed, randomised controlled trial is being conducted looking at measurable outcomes such as severity of pain using a visual analogue scale and the McGill Pain Questionnaire, restriction of range of motion of the shoulder joint and voluntary use of pain medication. Results of this high-quality study are hoped to provide evidence to show the effectiveness of acupuncture on painful shoulder [18].

Acupuncture for osteoarthritis Use of acupuncture for osteoarthritis of the knee is well accepted by practitioners and patients alike. Acupuncture needles are inserted into acupoints around and behind the knee. Some distant points around the ankles can also be used. Some of the common acupoints used for this condition are shown in Table 34.09. An earlier randomised trial of acupuncture as an adjunctive therapy in osteoarthritis of the knee involving 73 patients showed patients randomised to acupuncture improved on both Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and Lequesne indices compared with those who received standard treatment alone. Significant differences on the total WOMAC scale were seen at 4 and 8 weeks of treatment. However, the effect appears to decline 4 weeks after cessation of treatment [1]. Seven

trials representing over 300 patients with knee osteoarthritis were included in one study looking at pain and function after treatment. For pain, there was strong evidence that real acupuncture is more effective than sham acupuncture. For function, the evidence is inconclusive [7]. A Cochrane database systematic review in the year 2000 looked at the effect of transcutaneous electrical nerve stimulation (TENS) and acupuncture-like TENS (AL-TENS) on a total of 148 patients in the treatment group and 146 patients in the placebo group and concluded that TENS and AL-TENS are more effective in pain control compared with placebo and that sham acupuncture exerts similar effects similar to TENS [15].

Acupuncture for low back pain Acupuncture has been frequently used for nonspecific low back pain for quite some time. The advocates of this mode of treatment suggest that it is simple, safe and its effects are obvious. Apart from the traditional acupoints in the bladder meridian, new points along the spine are used frequently. Some of the common acupoints are shown in Table 34.10. Warm needling, using either moxibustion or shining infrared light onto the area of needling, achieves better effects. In order to study the available evidence for this form of treatment, the randomised trials of all types of acupuncture treatment which involved needling

556 Anne KWAN

Table 34.09

Some acupoints for osteoarthritis of the knee

Points

Location

Technique

SP 9 (Yinlingquan)

Depression of lower border of medial condyle of tibia

Straight insertion of 0.5 tsun deep

ST 35 (Dubi)

Depression at lateral lower border of patellar ligament

Straight insertion of 1 tsun deep

BL 40 (Weizhong)

Midpoint of transverse crease of popliteal fossa

Straight insertion of 1 tsun deep

LR 7 (Xiguan)

1 tsun behind SP 9

Straight insertion of 1 tsun deep

LR 8 (Quoquan)

Depression above medial end of transverse popliteal crease in a flexed knee

Straight insertion of 1 tsun deep

for subjects with this condition were reviewed [24]. Unfortunately only two out of the 11 randomised controlled trials met the high quality level required for inclusion in the review. The results of the review indicated that there was inadequate evidence showing acupuncture to be more effective than no treatment. Comparing acupuncture with trigger-point injection or TENS, there was moderate evidence indicating that acupuncture is more effective. One of the conclusions from the Table 34.10

review is that acupuncture is not recommended as a regular treatment for patients with low back pain. Despite the absence of positive evidence, acupuncture continues to be used in many cases. There is no question that it is an effective means of providing short-term pain relief. Use can be made of this effect to provide short-term pain relief to patients who suffer from major or moderate side effects of pain medications. Muscle strengthening physiotherapy may be provided

Some acupoints for low back pain

Points

Location

Technique

BL 23 (Shenshu)

1.5 tsun lateral to lower border of spinous process of L2

Straight insertion of 1 tsun deep

BL 25 (Dachangshu)

1.5 tsun lateral to lower border of spinous process of L4

Straight insertion of 1 tsun deep

BL 36 (Chengfu)

Middle of transverse gluteal fold

Straight insertion of 1.5 tsun deep

BL 37 (Yinmen)

6 tsun below BL 36 on line linking BL 36 and BL 40

Straight insertion of 1.5 tsun deep

BL 40 (Weizhong)

Midpoint of transverse crease of popliteal fossa

Straight insertion of 1 tsun deep

GB 30 (Huantiao)

At junction of lateral 1/3 & medial 2/3 distance between greater trochanter of femur and hiatus of sacrum

Straight insertion of 2 tsun deep

GB 39 (Xuanzhong)

3 tsun above tip of lateral malleolus of fibula

Straight insertion of 1 tsun deep

Ashi points

Tender spots where no important underlying structure is found

Straight insertion of 0.5–1 tsun

EX-BZ L2-4 (Jiaji)

0.5 tsun lateral to the lower border of spinous process from L2–4

Straight insertion of 1 tsun deep

Acupuncture and Traditional Chinese Medicine 557

without significant discomfort after a session of acupuncture. During acupuncture treatment, rapport between the patient and therapist can be built up. This can be a valuable building block for subsequent psychological and cognitivebehavioural management of the patient.

Acupuncture for other symptom relief The most convincing evidence of the efficacy of acupuncture treatment is the use of PC 6 (Neiguan) for treating nausea and vomiting, especially in the postoperative period. Quite a number of clinical trials have been conducted. A large randomised placebo controlled patient- and observer-blind trial conducted in the year 2002 tried to determine whether acupuncture at the acupoint PC 6 is effective in preventing postoperative nausea and vomiting (PONV) compared with placebo acupuncture. Over 200 female patients were randomly assigned to two groups. Although the study could not prove that acupuncture is more effective than placebo acupuncture in prevention of PONV in all patients, in a subgroup analysis PONV was reduced by acupuncture in patients after gynaecological surgery [21]. A systematic review of 26 trials involving 3,347 patients showed significant reductions in the risk of nausea, vomiting and the need for rescue antiemetics in the PC 6 acupoint stimulation group compared with the sham treatment group, although many of the trials were heterogeneous. The results of the systematic review supported the use of PC 6 acupoint stimulation in patients without antiemetic prophylaxis [11].

Other Forms of Acupuncture Ear acupuncture is a micro-acupuncture technique first described in French and Chinese medicine in 1950. It was speculated that the technique worked because groups of pluripotent cells contain information from the whole organism and create regional organisation centres representing different parts of the body. Stimulation of a reflex point can relieve symptoms of distant pathology [27]. Although ear acupuncture is one of the safest forms of acupuncture, if auricular press needles are used instead of steel spheres or auricular seeds, complications such as infection, bleeding and haematoma can still occur [23].

Scalp acupuncture has also been used for some years. Different acupoints on the scalp represent different parts of the body and stimulation of one or a group of acupoints can bring about relief of certain disease conditions. The most common condition in children treated by scalp acupuncture is cerebral palsy. Other forms of acupuncture are being developed with varying degrees of success. One currently being practised is tongue acupuncture.

Safety of Acupuncture Complementary methods, including acupuncture, are seen by many patients as less invasive, more natural and less liable to adverse effects than more orthodox forms of treatment. These were no more than just opinions until recent surveys provided some evidence. The early literature on the safety of acupuncture consisted entirely of case reports. Rampes and James summarised all case reports between 1966 and 1993, finding 395 instances of complications. Many were minor, such as bruising or fainting, but 216 were serious, including several cases of pneumothorax and injury to the spinal cord [17]. In another large survey, data collected over 2 years from 78 acupuncturists recorded 43 “significant” and 2,135 minor events, giving a rate of 14 and 671 per 10,000 respectively. There was no serious event reported. The most common events were bleeding (310 per 10,000 consultations), needling pain (200 per 10,000) and aggravation of symptoms (96 per 10,000). All adverse events had resolved within 1 week, except for one incident of pain that lasted 2 weeks and one of sensory symptoms that lasted several weeks [28]. Another study involved a prospective postal audit of treatments undertaken during a 4-week period in year 2000. A total of 574 practitioners participated. There was no report of serious events, defined as events requiring hospital admissions, leading to permanent disability, or resulting in death. Practitioners did, however, report 43 minor adverse events (1.3 per 1000 treatments). The most common events were severe nausea and fainting. Other events were mild bruising, bleeding and aggravation of existing symptoms after treatments [13]. A systematic review located nine surveys, which included nearly a quarter of a million treatments, and

558 Anne KWAN

showed that the most common adverse events from treatments were needle pain (1–45%), tiredness (2–41%) and bleeding (0.03–38%). Feelings of faintness and syncope were uncommon (0–0.3%). Feelings of relaxation were reported by as many as 86%. Pneumothorax was rare, occurring only twice in nearly a quarter of a million treatments [6]. The absence of serious adverse events is reassuring, but it is important to note the participants in these surveys would have received training in acupuncture [26]. Hence proper training in acupuncture is very important in keeping acupuncture a safe treatment modality. In order to minimise complications, contraindications such as local infection, bleeding tendency, distorted anatomy, tumour infiltration into or near acupoints must be excluded before needling. Extra caution must be taken when needling a patient who is very frail, anxious and hypertensive or hypotensive. Particular attention

must also be paid to patients with certain medical conditions such as diabetes, especially those complicated with peripheral circulation problems. It should be borne in mind that some acupoints may exert an effect on the blood-sugar level and this may not be desirable in diabetic patients. Electrical stimulation is not advisable in patients with an implanted cardiac pacemaker. Obviously, confused or unco-operative patients are unsuited to receive acupuncture treatment.

Conclusion This short summary on acupuncture provides an overview of the basic understanding of the application of this technique in pain management. Numerous text books and reference materials are available for readers who are interested in this form of therapy.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

Berman BM, Singh BB, Lao L, et al. A randomized trial of acupuncture as an adjunctive therapy in osteoarthritis of the knee. Rheumatology 1999;38:346–54. Birch S, Felt R, Lytle D. Understanding Acupuncture. Edinburgh: Churchill Livingstone, 1999:255–69. Carlsson C. Long-term effects of acupuncture. University of Lund, Sweden, 2000;1–10. Clement-Jones V, McLoughlin L, Tomlin S, et al. Increased beta-endorphin but not met-enkephalin levels in human cerebrospinal fluid after acupuncture for recurrent pain. Lancet 1980;2: 946–9. Ernst E, Pittler MH. The effectiveness of acupuncture in treating acute dental pain: A systematic review. Br Dent J 1998;184:443–7. Ernst E, White AR. Prospective studies of the safety of acupuncture: A systematic review. Am J Med 2001;110:481–5. Esso J, Hadhazy V, Birch S, et al. Acupuncture for osteoarthritis of knee: A systematic review. Arthritis Rheum 2001;44:819–25. Gellman H. Acupuncture Treatment for Musculoskeletal Pain – A Textbook For Orthopaedics, Anaesthesia and Rehabilitation. Miami:Taylor & Francis, 2002:28–31. Irnich D, Behrens N, Molzen H, et al. Randomised trial of acupuncture compared with conventional massage and “sham” laser acupuncture for treatment of chronic neck pain. BMJ 2001;30:1574–8. Kenner D. A taxonomy of acupuncture. Proceedings of the first symposium of the Society for Acupuncture Research, Bethesda, Maryland, 1994. Lee A, Done M. Stimulation of the wrist acupuncture point P6 for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev 2004;(3):CD003282. List T, Helkimo M. Acupuncture in the treatment of patents with chronic facial pain and mandibular dysfunction. Swedish Dental Journal 1987;11:83–92. MacPherson H, Thomas K, Walters S, et al. The York acupuncture safety study: Prospective survey of 34,000 treatments by traditional acupuncturists. BMJ 2001; 323:486–7. Melchart D, Linde K, Fischer P, et al. Acupuncture for recurrent headaches: A systematic review of randomized controlled trials. Cephalagia 1999;19:779–86. Osiri M, Welch V, Brosseau L, et al. Transcutaneous electrical nerve stimulation for knee osteoarthritis. Cochrane Database Syst Rev 2000;(4):CD002823.

Acupuncture and Traditional Chinese Medicine 559

16. Petti F, Bangrazi A, Liguori A, et al. Effects of acupuncture on immune response related to opioid-like peptides. J Tradit Chin Med 1998;18:55–63. 17. Rampes H, James R. Complications of acupuncture. Acup Med 1995;13:26–33. 18. Romli M, van der Windt D, Giovanzana P, et al. International research project to devise a protocol to test the effectiveness of acupuncture on painful shoulder. J Altern Complement Med 2000;6:281–7. 19. Rosted P. Practical recommendations for the use of acupuncture in the treatment of temporomandibular disorders based on the outcome of published controlled studies. Oral Dis 2001;7:109–15. 20. Shen J. Research on the neurophysiological mechanism of acupuncture: Review of selected studies and methological issues. J Altern Complement Med 2001;7:S121–7. 21. Streitberger K, Diefenbacher M, Bauer A, et al. Acupuncture compared to placebo-acupuncture for postoperative nausea and vomiting prophylaxis: A randomized placebo-controlled patient and observer blind trial. Anaesthesia 2004;59:142– 9. 22. Ulett GA, Han J, Han S. Traditional and evidence-based acupuncture: History, mechanism, and present status. South Med J 1998;91:1115–20. 23. Usichenko TI, Dinse M, Pavlovic D, et al. Hemorrhage after auricular acupuncture due to postoperative dilutional thrombocytopenia. Anesth Analg 2006;103:1333–4. 24. van Tulder MW, Cherkin DC, Berman B, et al. The effectiveness of acupuncture in the management of acute and chronic low back pain. A systematic review within the framework of the Cochrane Collaboration Back Review Group. Spine 1999;24:1113–23. 25. Vickers A, Zollman C. ABC of complementary medicine – Acupuncture. BMJ 1999;319:973–6. 26. Vincent C. The safety of acupuncture. BMJ 2001;323:467–8. 27. Wang SM, Peloquin C, Kain Z. The use of auricular acupuncture to reduce preoperative anxiety. Anesth Analg 2001;93:1178–80. 28. White A, Hayhoe S, Hart A, et al. Adverse events following acupuncture: Prospective survey of 32,000 consultations with doctors and physiotherapists. BMJ 2001;323:485–6. 29. World Health Organization (WHO) Traditional Medicine Unit. Guidelines on basic training and safety in acupuncture. Geneva: World Health Organization, 1999:1–30.

35

Anthony W.K. LAU, Leo C.T. CHEUNG

Physiotherapy

Introduction

INTRODUCTION PAIN MODULATION METHODS Electrotherapy Manual therapy Acupuncture Exercise therapy Hydrotherapy PHYSIOTHERAPY AND CHRONIC PAIN Passive treatment versus active approach Biopsychosocial model in physiotherapy practice Physiotherapy in a multidisciplinary pain programme Graded exercise Pacing skill Goal setting CONCLUSION REFERENCES

Many patients attending physiotherapy do so because of painful conditions such as backache. A variety of pain modulation methods are available to the physiotherapist as tools in the management of pain. Clinically, they are used to provide short-term pain relief to facilitate subsequent use of active treatment. The application of local heat and cryotherapy to areas of pain which result from musculoskeletal injury are two long-established but effective techniques. Other forms of electrotherapy widely applied in physiotherapy include transcutaneous electrical nerve stimulation (TENS), interferential therapy (IFT) and ultrasound. Physiotherapists also use mechanical means in treating painful conditions. Manual therapy is a typical example of such intervention. Well-known approaches in manual therapy include the Maitland method and the neuro-orthopaedic approach. Pain relief from manual therapy is achieved through active and passive mobilisation of the spinal and peripheral joints in order to “normalise” the physiological and accessory range of motion. Some manual techniques with a long history, such as myofascial release, have also been used in clinical practice. Increasingly around the globe, acupuncture is incorporated into physiotherapy practice as the technique becomes more accepted in Western medical practice. On the other side of the spectrum, active therapeutic exercises have long been integral parts of the pain management strategies in physiotherapy. Various types of exercise have been applied in the clinical setting. Apart from the classical categories of strengthening exercise, mobilisation exercise, stretching exercise and aerobic exercise, there has been a recent development of segmental and core stabilisation exercises of the spine. All these exercises can be practised on land as well as in the warm-water environment of hydrotherapy, where the soothing effect of the heated water has the added advantage of encouraging relaxation.

562 Anthony W.K. LAU, Leo C.T. CHEUNG

With growing evidence of the more effective approach of multidisciplinary team management of chronic painful conditions, physiotherapy has been systematically incorporated into many pain management programmes. Physiotherapists also increasingly recognise the importance of patients’ psychosocial and spiritual well-being. There is a trend towards cognitive-behavioural strategies in the training and clinical practice in physiotherapy.

Pain Modulation Methods Electrotherapy With the advancement of the gate control theory of pain following its proposal in the 1960s, there was a rapid development of different types of electrical stimulation for pain relief. Many of these stimulation modalities such as the Russian Faradic current, the high-voltage galvanic current and the micro-current lost popularity with time. Some modalities such as TENS and interferential current are still widely applied in physiotherapy. Both TENS and interferential current pass through tissues and cause nerve fibres to depolarise. The type of nerve influenced and the rate at which the fibre is depolarised will determine the physiological and therapeutic effect achieved [78]. The proposed mechanism of pain control includes activation of large alpha myelinated afferent nerve fibres which stimulate the substantia gelatinosa in the spinal cord, closing the “pain gate” on pain transmission to the thalamus. Release of endogenous opioids is also put forward as an explanation for the pain relief capacity of TENS and IFT. Finally, as with any other pain modulation modality, the placebo effect should always be taken into account [63]. The use of TENS of high frequency and long pulse duration is claimed to be more effective in pain modulation. Treatment is typically given for 15 minutes and upward; and using a modulated mode with a rhythmic up and down surge of current intensity is thought to discourage adaptation to the sensation. Typical interferential current stimulation uses two “medium frequency” currents of 3900 Hz and 4000 Hz. The resultant resonance “low frequency” current of 100 Hz at the cross area of the current vector is the therapeutic interferential current. The

therapeutic interferential current frequency can be varied to achieve pain reduction [39]. Correct electrode placement is important in order to stimulate the target nerves. Most physiotherapists apply the TENS and IFT electrodes in the immediate vicinity of the lesion. The four IFT electrodes are carefully placed to surround the target area so that the painful area is at the centre of the IFT current. The TENS and IFT electrodes can also be placed over the nerve trunk, spinal nerve root, within dermatomes and at acupuncture points. Interferential therapy is used primarily for acute musculoskeletal pain conditions [26]. Clinically, it provides a short-term pain modulation effect and is helpful in facilitating the subsequent application of active intervention such as exercise therapy. Although both TENS and IFT have been shown to be relevant in pain modulation, research to determine their efficacy tends to suggest that there is limited or inconsistent evidence to support their use as a single therapeutic intervention to provide long-term effectiveness in painful conditions [41, 45]. Other common electrotherapy agents such as ultrasound and extracorporeal shock wave therapy are used widely for soft tissue inflammatory and pain conditions. The ultrasound used in physiotherapy is usually of either 1 or 3 MHz. Ultrasound applied to inflamed tissue can enhance repair and healing. The mechanism is based on cellular excitation resulting from stable cavitation and an acoustic streaming effect. Ultrasound travels through tissues and is preferentially absorbed in dense collagenous tissues such as ligament, tendon and fascia. The mechanical energy absorbed may increase transmembrane cellular permeability to ions. Consequently, cells may become more excited physiologically. This enhanced cellular excitation enhances repair and healing. Ultrasound therapy administrated in continuous mode and relatively high intensity may produce a thermal effect. Local temperature at the insonated area may increase. The warmth generated may induce an increase in blood flow and facilitate repair and healing [78].

Physiotherapy 563

In summary, ultrasound therapy controls inflammation and regulates blood flow in the acute phase of injury. It stimulates fibroblastic action and collagen formation in the acute repair phase; and it improves collagen alignment and extensibility of mature collagen in the remodelling phase of the repair process [46]. Indications for extracorporeal shock wave therapy include chronic painful conditions. Treatment of plantar fasciitis and calcifying tendinitis of the shoulder rotator cuff has shown some promising results [38, 61]. High energy shock wave therapy appears to be more effective in improving the painful symptoms than low energy shock wave. However, calcific deposits remained unchanged in size after therapy [1, 23]. The mechanism of pain relief provided by extracorporeal shock wave is not completely understood. A high-energy dose of shock waves may selectively lead to dysfunction of the peripheral sensory unmyelinated nerve fibres without affecting motor nerve fibres. In low energy application, the shock waves may induce the release of neuropeptides such as calcitonin generelated peptide, which are thought to cause local neurogenic inflammation in the focal area. In turn, the inflammation may prevent the re-innervation of sensory nerve endings into the lesion area and contribute to clinically evident long-term analgesia [62].

Manual therapy Manual therapy in physiotherapy means manual application of passive mobilisation or manipulation to joints and soft tissues. One of the clinical indications is pain relief [72]. To reduce disability, handicap or to improve quality of life, it is often necessary to use manual therapy in conjunction with other treatment modalities [25, 54]. There are many ways to use manual therapy in physiotherapy, but the Maitland approach is one of the most commonly adopted by physiotherapists. The Maitland approach incorporates systematic assessment and treatment of the spinal and peripheral joints systems. The primary focus includes restoring physiological as well as accessory movement of joints. Well-controlled manual force is specifically directed to joints and soft tissues in a “hands-on” manner. For instance, with the patient lying in the prone position, manual force can be applied to the spinous process of a vertebra

to produce a posteroanterior gliding movement of that vertebral segment. Besides applying passive movement to joints and the surrounding soft tissue, passive neural mobilisation can also be applied in selected cases where there is restriction in the neurodynamics of the nervous system. The treatment is based on the theory that neural tissues in the nervous system move, stretch and slide during bodily movement. Restriction in the movement of neural tissue causes a chain reaction of pain and dysfunction. Normalisation of the neurodynamics through passive mobilisation of peripheral and spinal joints can bring about pain reduction. A classical example of mobilisation of neural tissue is the straight-leg raising manoeuvre to mobilise the sciatic nerve. The magnitude of force and the resulting movement can be broadly categorised as mobilisation and manipulation. Mobilisations use low-velocity, small- or large-amplitude passive movements within the patient’s range of motion and control. Manipulation is a localised force of high velocity and low amplitude directed at a joint at the extreme range of motion [51, 28]. Spinal manual therapy has been shown to be effective in providing pain reduction in patients with low back pain [18, 36, 37]. To improve the efficacy, it is suggested that appropriate patient screening and selection through systematic subjective and objective assessments are essential [34]. Moreover, manual therapy may benefit a subgroup of patients with spinal pain satisfying a predefined clinical prediction rule. Increasing research has helped identify patients most likely to respond positively to manual therapy using prediction rules [7, 10].

Acupuncture Acupuncture has become widely used in treatment of pain conditions. The possible mechanisms of action include activation of endogenous opioidrelated pain-inhibiting pathways through the peripheral nerve fibres and a profound alternation of local haemodynamics [82]. Physiotherapists adopt modern theories of neurophysiology in their application of acupuncture in pain management. Acupuncture is used as a treatment adjunct in a number of pain conditions, such as mechanical low back pain and degenerative

564 Anthony W.K. LAU, Leo C.T. CHEUNG

knee pain. In clinical practice, other treatments which restore function, such as a specific exercise, will usually be prescribed following acupuncture treatment [55, 84]. In the clinical setting, physiotherapists use both electro-acupuncture and manual needle manipulation to boost the pain relief effect. In selecting the stimulation parameters in electroacupuncture, usually both low-frequency and high-intensity stimulation are combined with high-frequency and low-intensity stimulation. Electro-acupuncture of low frequency, e.g. 2 to 4 Hz, and high intensity triggers slow onset of an endorphinergenic mechanism resulting in longlasting and cumulative pain reduction. Stimulation using high frequency, e.g. 80–100 Hz, and low intensity, on the other hand, provides a rapid onset in pain relief [60, 81]. The pain relief and functional enhancement are more pronounced in the short term [27].

Exercise therapy Exercise therapy has a wide application in physiotherapy. Exercise-based treatments aim to use the benefits of exercise to promote wellness rather than illness behaviour [47]. Exercise therapy can take many forms, depending on the effect desired. The therapy can include strengthening exercises to improve muscle power, mobilising exercises to improve the range of joint motion and stretching exercises to restore normal soft tissue length. The mechanism of pain reduction by exercise may involve intricate neurobiology in the central and peripheral system. The most widely discussed hypothesis for the mechanism of exercise-induced analgesia involves a central opioid mechanism. It has also been postulated, however, that activation of proprioceptive and muscle afferents inhibits the central pain circuitry. It has been shown that there is a threshold of afferent input which needs to be reached to inhibit central pain networks. Highintensity (around 70% VO2 max), long-duration (around 30 minutes) aerobic exercises tend to produce a more prominent pain relief effect than low-intensity, short-duration exercises [35, 44]. Moreover, intensive exercise programmes, alone or in combination with other treatments, which are specifically individualised are more beneficial than standardised programmess [53, 70].

In 1981, McKenzie proposed a classification system and a classification-based treatment for low back pain. So far, specific physiotherapy exercises have the greatest empirical support. McKenzie’s method places emphasis on correcting spinal dysfunction. It has been shown to provide short-term pain relief in acute low back pain [9]. A more recent systematic review re-iterates the importance of classifying patients with low back pain before assigning them to McKenzie exercise [49]. A more recent development in prescribing segmental and core stabilisation exercise for the treatment of spinal and pelvic pain has attracted academic and clinical attention. Isolated actions of the deep spinal muscles such as the transverse abdominus and multifidus are trained with or without biofeedback aids. Since such isolated actions are sometime difficult to comprehend, therapists are now beginning to look into the more dynamic exercises such as used in the Pilates exercise method, which also has a strong focus on core stabilisation. Clinical trials have been generally positive in affirming the pain relief provided by stabilisation exercises. Spinal-specific stabilisation exercises can be particularly useful in reducing cervicogenic headache and associated neck pain, chronic back pain, pelvic pain and recurrence after acute low back pain [5, 19, 25]. To perpetuate the benefits of exercise therapy, patients should be instructed to continue the exercises at home. Besides the content and the types of exercise, a patient’s compliance in persisting with the exercises at home is one of the key factors of success in pain management through active exercise therapy [6]. Physiotherapists should communicate well with the patients on the rationale of a home exercise regime and advise patients how to accommodate exercises in their everyday life. While the effect of exercise in reducing pain is supported in clinical research, available evidence does not show any consensus on the difference in the efficacy of different forms of exercise [52].

Hydrotherapy Water is a unique medium for rehabilitation. It is a particularly useful treatment option for patients with painful conditions [29]. Besides the buoyancy effect of the water, the warmth of the hydrotherapy pool (30–35°C) is soothing and induces relaxation

Physiotherapy 565

in many patients with musculoskeletal painful conditions. Moreover, the hydrostatic pressure exerted by the water helps patients in practising joint stabilisation. Hydrotherapy exercises have the same beneficial effects as land exercises in terms of physical fitness, pain relief and functional improvement [85]. They have the added value that many rehabilitation activities which patients find painful to carry out on land can be safely and comfortably managed in water. For instance, patients with pain from osteoarthritic knees can benefit from a hydrotherapy work-up to improve the power and range of their lower limbs, as well as their cardiovascular capacity. Land drill of a similar intensity may be too painful. Recently, different types of exercise methods have been introduced into hydrotherapy. Water Tai chi, water yoga and water Pilates are examples of such “fusion”. Water Tai chi improves balance and co-ordination. The warm water in hydrotherapy facilitates relaxation which is required in yoga, while the hydrostatic pressure of water enhances the effect of stabilisation to the spine in Pilates. Patients’ response to hydrotherapy is encouraging. After a period of hydrotherapy exercise, many patients have a decrease in their pain level and an improvement in sleep quality. Patients with rheumatic arthritis completing a course of hydrotherapy have reported feeling much better or very much better than when treated with land exercises [16]. Hydrotherapy has been shown to be an effective pain management regimen [11, 69].

Physiotherapy and Chronic Pain Passive treatment versus active approach Available evidence suggests that passive pain modulating procedures such as TENS, heat/ cold, traction, laser, ultrasound, shock wave and interferential current therapy may not be effective in the management of the chronic pain syndrome. In a recent review, the author identified six systematic reviews and four randomised controlled trials on acupuncture, TENS and laser

therapy in the management of chronic pain [17]. He concluded that the evidence for efficacy in these treatment methods when used for chronic pain was contradictory or inadequate. Nordin and Campello (1999) concluded that although there was no evidence of efficacy, high patient satisfaction was associated with their use [58]. The authors suggested that one way to resolve the dilemma is to teach the patient self-application of these procedures for short-term pain relief. They also suggest that patients should be informed that passive methods are much less effective than more active treatments and that adopting a self-managed active therapeutic exercise routine is necessary to achieve better and longer-lasting effects.

Biopsychosocial model in physiotherapy practice Treating patients with chronic pain is one of the most challenging tasks in everyday physiotherapy practice. In chronic syndromes, physical dysfunction and psychosocial issues are factors of equal importance in influencing the patient’s response to physiotherapy treatment and rehabilitation. Chronic pain management requires an integrated biopsychosocial approach to achieve a favourable outcome. It is well recognised that a multidisciplinary approach works better than single specialty intervention [4, 54]. The biopsychosocial model was proposed by Waddell [76]. It highlights the interaction of pain, attitudes and beliefs, psychological stress, illness behaviour and social environment which affect the patient’s response to treatment and rehabilitation. An understanding of the biopsychosocial model and the subsequent integration of cognitivebehavioural principles into physiotherapy have led to some quite significant changes and improvements in practice [32, 57]. In patients with chronic pain and associated disability problems, physiotherapists are now being encouraged to actively screen for, identify and then appropriately tackle relevant psychosocial components [50, 77]. A number of key psychological factors can create a barrier to recovery. These include the presence of a belief that pain is harmful or severely disabling; fear-avoidance behaviour patterns with a reduction in activity levels; a tendency to mood lowering and withdrawal from

566 Anthony W.K. LAU, Leo C.T. CHEUNG

social interaction; and an expectation that passive treatment rather than active participation will help. In a recent study, Woby and his colleagues have clearly shown that there was a strong association between cognitive factors and the levels of pain and disability in 183 chronic low back patients who presented for physiotherapy [80]. Functional self-efficacy emerged as a particularly strong predictor of both pain intensity and disability. In view of their findings, it would seem that targeting specific cognitive factors should be an integral facet of physiotherapy-based treatments for chronic low back pain patients. Cognitive approaches to chronic pain focus on the way the person perceives, interprets and relates to pain rather than the elimination of pain [79]. In the implementation of the cognitive-behavioural approach in physiotherapy practice, therapists assist the chronic pain patient to confront the fearavoidance response, which leads to the reduction of fear and an increase of physical activities. Once selfefficacy has improved, fear-avoidance behaviour becomes reduced and daily functioning can be escalated. In chronic back and neck pain conditions, there is evidence suggesting that cognitive-behavioural interventions can be successful [14, 15, 48]. The increased effectiveness of physiotherapy with additional training to enhance communication skills and the incorporation of cognitive-behavioural strategies in everyday practice has been evaluated in a few trials [68, 42]. The results have demonstrated varying degrees of success. Another pilot programme in which physiotherapists were trained to deliver physical treatment using cognitive-behavioural strategies has shown encouraging results in the primary care setting [33, 40]. The extent of training and skill levels which are required to deliver an effective cognitive-behavioural intervention may also be critical.

Physiotherapy in a multidisciplinary pain programme Multidisciplinary treatment programmes for patients with pain conditions aim to improve function and help them to cope with their symptoms. They involve different health care professionals and mainly consist of intensive physical

and psychosocial components including education, active exercise programmes, cognitive-behavioural interventions, relaxation, and workplace visits and job modification. The main role of the physiotherapist in the team is to co-operate with other disciplines in using a cognitive-behavioural approach to help patients adopt regular exercise into their daily lives so as to improve or maintain physical functioning, and thus prevent further disuse or disablement. All health care professionals in the team deliver the same message regarding the diagnosis and prognosis of the pain condition, encouraging a gradual return to normal activities. Patients need to be clear that although movement may hurt, it does not mean that any damage is occurring. They should be encouraged to return to their usual activities even the pain is not completely resolved. Minimising the use of medication for pain control and health care system services is another key success of the programme. Multidisciplinary therapy based on intensive exercises improves physical function and has a modest effect on pain [4]. Tulder in 2000 identified 10 randomised clinical trials (n=1,691) assessing multidisciplinary treatment programmes in the management of chronic low back pain [71]. The trials provided strong evidence that multidisciplinary treatment programmes had better outcomes on pain, functional status and sick leave than other conservative treatments for up to 1 year after treatment. Programmes lasted mostly for 3 weeks and were given to groups of 10 to 12 patients. In a recent exploratory retrospective cohort study, De Blécourt recruited 70 children and adolescents (aged 8–21 years) with chronic musculoskeletal pain to a 3-month inpatient multidisciplinary pain management programme [12]. The programme comprised graded physical exercises, graded activities and counselling of the children and their parents. Motor and social activities, pain intensity, global assessment of physical functioning and psychosocial well-being, understanding of the pain process and reduction of medical consumption were measured. Results showed that there were significant improvements in motor performances, school attendance, reduction of pain scores, an understanding of the chronic pain process and reduction of medication consumption when the

Physiotherapy 567

pre- and post-programme data were compared. Results remained stable at follow-up after 3 months. The authors concluded that a multidisciplinary pain management programme for children and adolescents with chronic musculoskeletal pain could be effective. A recent Cochrane database systematic review provided evidence that intensive multidisciplinary biopsychosocial rehabilitation with a functional restoration approach improves pain and function; less intensive interventions did not show improvements in clinically relevant outcomes [30]. In another recent systematic review of nonpharmacological therapies for acute and chronic low back pain for the American Pain Society/American College of Physicians clinical practice guideline, the authors assessed benefits and harms in a wide range of treatment procedures and approaches [8]. They included acupuncture, back schools, psychological therapies, exercise therapy, functional restoration, interdisciplinary therapy, massage, physical therapies (IFT, low-level laser therapy, lumbar supports, shortwave diathermy, superficial heat, traction, TENS and ultrasonography), spinal manipulation and yoga for acute or chronic low back pain. The authors concluded that therapies with good evidence of moderate efficacy for chronic low back pain are cognitive-behavioural therapy, exercise and interdisciplinary rehabilitation [8]. The interdisciplinary approach in chronic pain programmes requires a large degree of cross-working within the team as it is desirable and necessary to ensure a consistent and coherent treatment. A thorough understanding of the methods of the other team members is necessary. In a standardised 4-week inpatient, structured interdisciplinary pain rehabilitation programme for patients with fibromyalgia or chronic back pain which covered elements of cognitive- and operantbehavioural therapy, graded activity exercises and adapted drug therapy, results showed that physical and social function, pain reduction, mood and coping skill were significantly improved postprogramme and at the 6-month follow-up [2].

Graded exercise Exercise is one of the key components in any rehabilitation programme for patients with chronic

pain. Exercise programmes should begin with a stretching routine to lengthen tight muscle groups, be followed with a strengthening component to tone up disused muscles and incorporate sessions of aerobic exercise to build up cardiopulmonary fitness. Specific therapeutic exercises should be tailor-made for chronic pain patients according to their personal set of functional goals. Evidence is particularly strong for the effects of exercise in chronic pain patients, in particular for improvement in aerobic endurance and pain reduction [43, 65]. However, patients with chronic pain usually exhibit marked fear avoidance, low self-efficacy and high-pain intensity during movement or exercise. Previous studies have revealed that self-efficacy was more strongly related to pain and disability than pain-related fear [3, 13]. The physiotherapist can reactivate patients to do exercises by means of graded exposure. This means that any exposure to exercise should be gradual and increases must be by negotiation with the physiotherapist but in the control of the patient. The original model for graded exercise was proposed by Fordyce in 1976 [21]. Using this method, patients are instructed to find a baseline tolerance level for each exercise. To begin with, they perform the exercise below the baseline, in other words below each patient’s limit. For any patient who is disabled and/or exhibits strong fear avoidance, the baseline may simply mean contemplating an exercise, or adopting the exercise starting position. Once improvement is noted, the patient is encouraged to step up and gradually escalate the drill above the baseline. In this way, the control over the exercise behaviour is contingent upon plan rather than pain. This general model can be applied to all exercises. Through this agreed graded progression and described pathway, patients with chronic pain can restore their physical confidence, decrease their fear avoidance and improve self-efficacy. Studies have shown that gradually exposing patients to activities which they perceive as threatening or even harmful is an effective form of treatment for chronic low back pain in patients who exhibit an elevated painrelated fear [74, 75]. In a recent study, 44 chronic low back pain patients were randomly assigned to graded activity in vivo exposure, or to wait-list control. Patients in the graded activity group demonstrated significantly greater improvements on measures of fear of pain/

568 Anthony W.K. LAU, Leo C.T. CHEUNG

movement, fear-avoidance beliefs, pain-related anxiety, pain catastrophising and pain self-efficacy when compared with those in the wait-list control group [83]. The authors commented that this principle could be applied also in conditions of acute low back pain.

Pacing skill Overdoing and under-doing activities are very common in chronic pain patients [66]. Patients may not do activities or exercise when their pain level is high (bad days), but can overdo activities or exercise when their pain level is low (good days).

By means of graded therapeutic exercise and pacing skills to build up physical strength and endurance, sitting tolerance or gait performance, goals can be achieved in a defined time frame. At the same time, goal setting allows development of a sense of purpose and gives a baseline for reviewing progress [64]. Regular review and refining of set goals with chronic pain patients should be encouraged in order to meet their individual short and long term needs.

Conclusion

Pacing is the systematic increase in activity tolerance using the principle of carrying out a steady realistic mixture of activities and breaks, with activities being increased by quota [32]. Its aim is to even out the peaks and troughs of activities which are affected by pain level [31] and it counteracts overdoing or under-doing activities. Through the pacing skill, activities are restructured and regulated by time, sequence or quotas. Patients with chronic pain need to develop their own set of activity-pacing principles by planning and prioritising activities, setting a baseline, breaking tasks into smaller steps, taking regular short breaks or rest, increasing or decreasing the specific activities or exercises in a gradual and controlled manner. An activities/exercise logbook can also act as a self-reinforcement tool and allows patients to quantify their progress.

Physiotherapy has wide range of application in the management of pain from the acute to the persistent chronic pain syndrome. The role of the physiotherapist includes giving advice on selfmanagement, screening and triaging in primary care, effecting pain modulation to facilitate physical function restoration and establishing a specific exercise programme for each chronic pain patient.

Goal setting

While the benefits of adding a behavioural component to exercise programmes has yet to be consolidated [59], the physiotherapy profession has the potential to shift the modality of care from the narrow biomedical to a much broader holistic approach. With additional training in cognitivebehavioural strategies, physiotherapists may introduce new treatment strategies to address the needs of patients afflicted with chronic pain.

Through systematic assessment and patient selection, physiotherapists can provide information on patients’ physical and functional capacity to the multidisciplinary team. The information is useful in setting goals and coping strategies for the patients. Identification and specification of goals is the basis for addressing an increase in activities [32]. Goals should be set as attainable, personally relevant and measurable as possible, and can be functional tasks relating to everyday activities such as walking without aids for a prescribed distance, or sitting for a definite time to do a specific task. Patients can work together with the physiotherapist to break down the goal into several blocks.

Experience in the integrated multidisciplinary approach often helps physiotherapists to re-visit the once-dominant thinking that a specific pain source and injured tissue must be present and identified [24]. Physiotherapists increasingly witness the important interplay of the physical-psycho-socialspiritual dimensions of pain.

Emerging evidence will help the physiotherapy profession to arrive at the best practice model in which there is concerted collaboration with other health disciplines to bring about functional restoration and improved quality of life in pain patients.

Physiotherapy 569

References 1. 2. 3. 4. 5. 6. 7. 8.

9. 10.

11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.

Albert JD, Meadeb J, Guggenbuhl P, et al. High energy extra-corporeal shock wave therapy for calcifying tendinitis of the rotator cuff: A randomised trial. J Bone Joint Surg (Br) 2007;89:335–41. Angst F, Brioschi R, Main C J, et al. Interdisciplinary rehabilitation in fibromyalgia and chronic back pain: A prospective outcome study. J Pain 2006;7(11):807–15. Ayre M, Tyson GA. The role of self efficacy and fear avoidance beliefs in the prediction of disability. Aust Psychol 2001;36:250–3. Bodduk N. Management of chronic low back pain. Med J Aust 2004;180:79–83. Cairns MC, Foster NE, Wright C. Randomised controlled trial of specific spinal stabilisation exercises and conventional physiotherapy for recurrent low back pain. Spine 2006;31:670–81. Campell R, Evans M, Tucker M, et al. Why don’t patients do their exercises? Understanding non-compliance with physiotherapy in patients with osteoarthritis. J Epidemiol Community Health 2001;55:132–8. Childs JD, Fritz JM, Flynn TW, et al. A clinical prediction rule to identify patients with low back pain most likely to benefit from spinal manipulation: A validation study. Ann Intern Med 2004;141:920–8. Chou R, Huffman LH, for American Pain Society and American College of Physicians. Non-pharmacologic therapies for acute and chronic low back pain: A review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med 2007;147(7):492–504. Clare HA, Adams R, Maher CG. A systematic review of efficacy of McKenzie Therapy in management of back pain. Aust J Physiother 2004;50:209–16. Cleland JA, Childs JD, Fritz JM, et al. Development of a clinical prediction rule for guiding treatment of a subgroup of patients with neck pain: Use of thoracic spine manipulation, exercise, and patient education. Phys Ther 2007;87(1):9– 15. Dagfinrud H, Kvien TK, Hagen KB. The Cochrane review of physiotherapy interventions for ankylosing spondylitis. J Rheumatol 2005:32:1899–906. De Blécourt A, Preuper HS, Van Der Schans CP, et al. Preliminary evaluation of a multidisciplinary pain management program for children and adolescents with chronic musculoskeletal pain. Disabil Rehabil 2007;22:1–8. Denison E, Asenlof P, Lindberg P. Self-efficacy, fear avoidance, and pain intensity as predictors of disability in subacute and chronic musculosketetal pain patients in primary health care. Pain 2004;111(3):245–52. European Commission. European guidelines for the management of acute low back pain. Research Directorate General, European Commission COST Action B13, 2004. Available at www.backpaineurope.org. European Commission. European guidelines for the management of chronic low back pain. Research Directorate General, European Commission, COST Action B13, 2004. Available at www.backpaineurope.org. Eversden L, Maggs F, Nightingale P, et al. A pragmatic randomised controlled trial of hydrotherapy and land exercises on overall well being and quality of life in rheumatoid arthritis. BMC Musculoskelet Disord 2007;8:23. Fargas-Babjak A. Acupuncture, transcutaneous electrical nerve stimulation, and laser therapy in chronic pain. Clin J Pain 2001;17:105–13. Ferreira ML, Ferreira PH, Latimer J, et al. Efficacy of spinal manipulative therapy for low back pain of less than three months’ duration. J Manipulative Physiol Ther 2003;26(9):593–601. Ferreira PH, Ferreira ML, Maher CG, et al. Specific stabilisation exercise for spinal and pelvic pain: A systematic review. Aust J Physiother 2006;52(2):79–88. Fisher K, Hardie RJ. Goal attainment scaling in evaluating a multidisciplinary pain management programme. Clin Rehabil 2002;16(8):871–7. Fordyce WE. Behavioral Methods for Chronic Pain and Illness. St. Louis: CV Mosby Co., 1976:168–83. George SZ, Fritz JM, Bialosky JE, et al. The effect of a fear-avoidance-based physical therapy intervention for patients with acute low back pain: Results of a randomized clinical trial. Spine 2003;28(23):2551–60. Gerdesmeyer L, Wagenpfeil S, Haake M, et al. Extra-corporeal shock wave therapy for the treatment of chronic calcifying tendinitis of the rotator cuff: A randomised controlled trial. JAMA 2003;290(19):2573–80. Gifford L, Thacker M, Jones MA. Physiotherapy and pain. In McMahon S, Koltzenburg M, eds. Wall and Melzack’s Textbook of Pain, 5th edn. London: Churchill Livingstone Elsevier, 2005:603–17. Goldby LJ, Moore AP, Doust J, et al. A randomised controlled trial investigating the efficiency of musculoskeletal physiotherapy on chronic low back disorder. Spine 2006;31(10):1083–93. Gracey JH, McDonough SM, Baxter GD. Physiotherapy management of low back pain: A survey of current practice in North Ireland. Spine 2002;27(4):406–11. Green S, Buchbinder R, Hetrick S. Acupuncture for shoulder pain. Cochrane Database Syst Rev 2005;(2):CD005319. Gross AR, et al. Manipulation and mobilisation for mechanical neck disorder. Cochrane Database Syst Rev 2004;(1): CD0044249.

570 Anthony W.K. LAU, Leo C.T. CHEUNG

29. Gusi N, Thomas-Carus P, Hakkinen A, et al. Exercise in waist-high warm water decreases pain and improves healthrelated quality of life and strength in the lower extremities in women with fibromyalgia. Arthritis Rheum 2006;55:66– 73. 30. Guzmán J, Esmail R, Karjalainen K, et al. Multidisciplinary bio-psycho-social rehabilitation for chronic low-back pain. Cochrane Database Syst Rev 2007;18(3):CD000963. 31. Harding V, Simmonds MJ, Watson P. Physical therapy for chronic pain. In Pain —Clinical Updates. Seattle: IASP Press, 1998;6(3):1–4. 32. Harding V, Williams A. Extending physiotherapy skills using a psychological approach: Cognitive-behavioural management of chronic pain. Physiotherapy 1995;81(11):681–8. 33. Hay EM, Mullis R, Lewis M, et al. Comparison of physical treatments versus a brief pain management programme for back pain in primary care: A randomised clinical trial in physiotherapy practice. Lancet 2005;365:2024–30. 34. Hing WA, Reid DA, Monaghan M. Manipulation of the cervical spine. Manual Ther 2003;8(1):2–9. 35. Hoffman MD, Shepanski MA, Ruble SB, et al. Intensity and duration threshold for aerobic exercise-induced analgesia to pressure pain. Arch Phys Med Rehabil 2004;85:1183–5. 36. Hoving JL, de Vet HC, Koes BW. Manual therapy, physical therapy, or continued care by the general practitioner for patients with neck pain. Clin J Pain 2006;22(4):370–7. 37. Hurley DA, McDonough SM, Dempster M, et al. A randomised clinical trial of manipulative therapy and interferential therapy for acute low back pain. Spine 2004;29(20):2207–16. 38. Hyer CF, Vancourt R, Block A. Evaluation of ultrasound-guided extra-corporeal shock wave therapy (ESWT) in the treatment of chronic plantar fasciitis. Foot Ankle Surg 2005;44(2):137–42. 39. Johnson MJ, Tabasam G. An investigation into the analgesic effect of interferential currents and transcutaneous nerve stimulation on experimentally induced ischaemic pain in otherwise pain-free volunteers. Phys Ther 2003;83(3):208– 17. 40. Johnson RE, Jones GT, Wiles NJ, et al. Active exercise, education, and cognitive behavioural therapy for persistent disabling low back pain. Spine 2007;32(15):1578–85. 41. Khadilar A, Milne S, Brosseau L, et al. Transcutaneous electrical nerve stimulation for the treatment of chronic low back pain: A systematic review. Spine 2005;30(23):2657–66. 42. Klaber Moffett JA, Jackson DA, Richmond S, et al. Randomised trial of a brief physiotherapy intervention compared with usual physiotherapy for neck pain patients: Outcomes and patients’ preferences. BMJ 2005;330(7482):75. 43. Klepper SE. Effects of an eight-week physical conditioning program on disease signs and symptoms in children with chronic arthritis. Arthrit Care Res 1999;12:52–60. 44. Koltyn KF. Exercise-induced hypo-algesia and intensity of exercises. Sports Med 2002;32(8):477–8. 45. Kroeling P, Gross A, Goldsmith CH. A Cochrane review of electrotherapy for mechanical neck disorders. Spine 2005;30(21):641–8. 46. Leung M, Ng G. The effect of ultrasound on acute inflammation of transected medial collateral ligaments. Arch Phys Med Rehabil 2004;(85):963–6. 47. Liddle SD, Baxter GD, Gracey JH. Exercise and chronic low back pain: What works? Pain 2004;107:176–90. 48. Linton S, Andersson M. Can chronic disability be prevented? A randomised trial of a cognitive-behavior intervention and two forms of information for patients with spinal problems. Spine 2000;25:2825–35. 49. Machado LAC, de Souza MS, Ferreira PH, et al. The McKenzie Method for low back pain. Spine 2006;31(9):254–62. 50. Main CJ, Watson PJ. Psychological aspect of pain. Manual Ther 1999;4(4):203–15. 51. Maitland GD, et al. Maitland’s Vertebral Manipulation, 6th edn. New York: Churchill Livingstone, 2001. 52. Mannion AF, Muntener M, Taimela S, et al. A randomised clinical trial of three active therapies for chronic low back pain. Spine 1999;1(24):2435–48. 53. McNeely ML, Torrance G, Magee DJ. A systematic review of physiotherapy for spondylolysis and spondylolisthesis. Manual Ther 2003;8(2):80–91. 54. Moffett J, McLean S. The role of physiotherapy in the management of non-specific back pain and neck pain. Rheumatology 2006;45(4):371–8. 55. Mukherjee M, McPeak LK, et al. The effect of electro-acupuncture on spasticity of the wrist. Arch Phys Med Rehabil 2007;(88):159–66. 56. Muncey H. The challenge of change in practice. In Gifford L, ed. Topical Issues in Pain, 2. Biopsychosocial Assessment and Management. Relationships and Pain. Falmouth: CNS Press, 2000:37–54. 57. Muncey H. The biopsychosocial approach and low back pain. In Gifford L, ed. Topical Issues in Pain, 4. Placebo and Nocebo. Pain Management. Muscles and Pain. Falmouth: CNS Press, 2000:147–56. 58. Nordin M, Campello M. Physical therapy. Exercises and the modalities: When, What and Why? Neurol Clin 1999;17:76–89. 59. Ostelo RW, van Tulder MW, Vlaeyen JW, et al. Behavioural treatment for chronic low back pain. Cochrane Database Syst Rev 2005;(1):CD002014.

Physiotherapy 571

60. Pian Smith MCM, Pham LHT, Smith FWK. The neurophysiologic basis of acupuncture. In Gellman H, ed. Acupuncture Treatment for Musculoskeletal Pain: A Textbook for Orthopaedics, Anesthesia, Rehabilitation. New York: Taylor & Francis, 2002:8–27. 61. Roehrig GJ, Baumhauer J, Digiovanni BF, et al. The role of extra-corporeal shockwave on plantar fasciitis. Foot Ankle Clin 2005;10(4):699–712. 62. Rompe JD, et al. Repetitive low-energy shock wave application without local anesthesia is more efficient than repetitive low energy shock wave application with local anesthesia in the treatment of chronic plantar fasciitis. J Orthopaed Res 2005;(23):931–41. 63. Cuccurullo S, et al. Physical modalities, therapeutic exercise, extended bed rest, and aging effects. In Physical Medicine and Rehabilitation Board Review. New York: Demos Medical Publishing Inc., 2004. 64. Schmitz U, Saile H, Nigles P. Coping with chronic pain: Flexible goal adjustment as an interactive buffer against painrelated distress. Pain 1996;67(1):41–51. 65. Sherry DD, Wallace CA, Kelly C, et al. Short and long term outcomes of children with complex regional pain syndrome type treated with exercise therapy. Clin J Pain 1999;15(3):218–23. 66. Simmonds MJ and Peat JH. Rehabilitation therapies in pain and disability management. An activity driven biopsychosocial model of practice. In Tollison CD, et al., eds. Practical Pain Management, 3rd edn. Philadelphia Lippincott Williams & Wilkins, 2002:120–34. 67. Spenkelink CD, Hutten MMR, Hermens HJ. Assessment of activities of daily living with an ambulatory monitoring system: A comparative in patients with chronic low back pain and nonsymptomatic controls. Clin Rehabil 2002;16(1):16– 26. 68. Staal JB, Hlobil H, Twisk JW, et al. Graded activity for low back pain in occupational health care: A randomised, controlled trial. Ann Intern Med 2004;140:77–84. 69. Stener-Victorin E, Kruse-Smidje C. Comparison between electro-acupuncture and hydrotherapy, both in combination with patient education and patient education alone, on the symptomatic treatment of osteoarthritis of the hip. Clin J Pain 2004;20(3):179–85. 70. Taylor NF, Dodd KJ, Shields N, et al. Therapeutic exercise in physiotherapy practice is beneficial: A summary of systematic reviews 2002–2005. Aust J Physiother 2007;53(1):7–16. 71. van Tulder M, Koes B, Assendelft W, et al. Chronic low back pain: Exercise therapy, multidisciplinary programmes, NSAIDs, back schools and behavioural therapy effective; traction not effective; results of systemic reviews. Ned Tijdschr Geneeskd 2000;144 (31):1489–94. 72. Vernon H, Humphreys K, Hagino C. Chronic mechanical neck pain in adults treated by manual therapy: A systematic review of change scores in randomised clinical trials. J Manip Physiol Ther 2007;30(3):215–7. 73. Harding VR, Williams AC. Activities training: Integrating behavioral and cognitive methods with physiotherapy in pain management. J Occup Rehabil 1998;8(1):47–60. 74. Vlaeyen JWS, Linton SJ. Fear-avoidance and its consequence in chronic musculoskeletal pain: A state of the art. Pain 2000;85(3):317–32. 75. Vlaeyen JW, de Jong J, Geilen M, et al. The treatment of fear of movement/(re)injury in chronic low back pain: Further evidence on the effectiveness of exposure in vivo. Clin J Pain 2002;18: 251–61. 76. Waddell G. A new clinical model for the treatment of low back pain. Spine 1987;12:632–44. 77. Watson P, Kendall N. Assessing psychosocial yellow flags. In Gifford LS, ed. Topical Issues in Pain, 2. Biopsychosocial Assessment and Management. Relationships and Pain. Falmouth: CNS Press, 2000:111–29. 78. Watson T. The role of electrotherapy in contemporary physiotherapy practice. Manual Ther 2000;5(3):132–41. 79. Weisenberg M. Cognitive aspects of pain and pain control. Int J Clin Exp Hypn 1998;46:44–61. 80. Woby SR, Roach NK, Urmston M, et al. The relation between cognitive factors and levels of pain and disability in chronic low back pain patients presenting for physiotherapy. Eur J Pain 2007;11(8):869–77. 81. Wong AMK, Tang SFT, Lew HL. Acupuncture in the management of neuron-musculoskeletal disorders. In Shankar K, Randall KD, eds. Therapeutic Physical Modalities. Philadelphia: Hanley & Belfus, 2002:227–38. 82. Wong R, Lee TW, Sihoe A, et al. Analgesic effect of electroacupuncture in post-thoracotomy pain: A prospective randomised trial. Ann Thorac Surg 2006;81:2031–6. 83. Woods MP, Asmundson GJ. Evaluating the efficacy of graded in vivo exposure for the treatment of fear in patients with chronic back pain: A randomized controlled clinical trial. Pain 2008;136(3):271-80. Epub 2007 Aug 22. 84. Yeung CK, Leung MC, Chow DH. The use of electro-acupuncture in conjunction with exercise for the treatment of chronic low back pain. J Altern Complem Med 2003;9(4):479–89. 85. Yozbatiran N, Yildirim Y, Parlak B. Effect of fitness and aquafitness exercises on physical fitness in patients with chronic low back pain. Pain Clinic 2004;16(1):35–42.

36

Chetwyn C. H. CHAN, Connie Y. Y. SUNG

Occupational Therapy for Chronic Pain: Enhancement of the Role of Productivity and Return to Work

Introduction

INTRODUCTION CASE STUDY THE OCCUPATIONAL THERAPY PROCESS ERGONOMICS AND BIOMECHANICAL APPROACH COGNITIVE BEHAVIOURAL APPROACH CONCLUSION REFERENCES

Occupational therapy is a health care discipline which specialises in using daily activities as the media of treatment and engagement as the process to facilitate individuals with disabilities to participate in their life roles [5, 9, 40]. Alongside daily activities such as self-care and work, occupational therapists use technology, assistive devices and the environment in which the individual lives in order to achieve their therapeutic goals. Participation is an important concept in occupational therapy practice, as it maximises both the individual’s physical and mental potential to re-engage in his or her previous life roles and to develop new life roles [13, 19]. Occupational therapy practice, therefore, covers a wide range of both clientele and therapeutic aims. In this chapter, the focus is on describing how occupational therapy can help to re-engage clients who suffer from chronic pain by maximising their independence in self-care and productivity. Pain can take many forms, from acute to chronic and from sharp to dull. Acute pain is pain that lasts for a relatively short time; that is, a few days to a week. Chronic pain is pain that lasts for 3 to 6 months or more. It is this chronicity which can have serious negative effects on an individual’s life. The causes and mechanism of chronic pain have already been covered in other chapters of this book and hence are not repeated here. It is very common for chronic pain to result in a person’s lowering of functional capacity, feelings of fatigue and interrupted sleeping patterns. The consequences often impact on engagement in life and have a negative effect on emotional and psychological well-being [16, 35], causing depression, anxiety, anger, stress and loneliness [4]. Disengaging in life’s activities, in particular in work and social life, can result in low self-esteem, a distorted self-image, social isolation and

574 Chetwyn C. H. CHAN, Connie Y. Y. SUNG

low life-satisfaction [3, 10, 26, 34, 37]. The goal of occupational therapy is, therefore, to break this biopsychosocial vicious cycle by re-engaging individuals in their work and social roles, improving their physical and mental capability, and facilitating the recovery of role satisfaction and psychological well-being. The complex nature of chronic pain makes a team approach to clinical management a necessity [15, 36]. Such clinical management teams usually comprise of medical doctors, nurses, occupational therapists, physical therapists, psychologists and social workers. Each member in this multidisciplinary programme has unique skills to contribute to the total care of the client. This chapter will describe the unique role of the occupational therapist and the common theoretical models that form the basis of the clinical interventions used. To facilitate the reader’s understanding of the occupational therapy process, the case of Mr. Lee will be presented to illustrate such a process.

Case Study Mr. Lee was a 39-year-old restaurant chef when he was involved in an accident at work which resulted in severe back pain. He was admitted to a hospital emergency room and transferred to an orthopaedic ward. He was observed for 2 days on the ward and then discharged after being prescribed pain relief medications, physiotherapy and back care. He was later also referred to a return-to-work programme in an occupational therapy department. During the 8-week period of occupational therapy, he was involved in work hardening, training in workrelated ergonomics and occupational health, pain management, work skills retraining, work coaching with a work trial at a company and vocational counselling. Throughout the intervention, his pain level was monitored and he was taught different ways of coping with the residual pain while also engaging in the training. At the beginning of this intervention, Mr. Lee was considerably preoccupied with the pain he had in his lower back. His general health and functioning were found to have deteriorated, and he was only able to carry out basic self-care activities. The occupational therapist worked together with others of the professional team, such as the physician, physiotherapist and clinical psychologist, to help Mr. Lee realise his life roles, in particular his work

role. The occupational therapist worked with Mr. Lee to develop goals and to devise different strategies for achieving these goals within 8 weeks. Previous studies have indicated that any work rehabilitation programme should commence as early as possible and target the promotion of both general health status and job-related skills [42]. These studies also reported that injured workers who did not return to work within 6 months tended to develop chronicity, raising psychological issues. It was, therefore, deemed necessary to look at the employment requirements at the beginning of the programme. In view of this, Mr. Lee was immediately involved in a series of standardised or individualised physical, mental and simulated tasks using various functional capability battery tests and norms [20, 21, 22]. All findings were crossmatched with the job demand profile developed for Mr. Lee in consultation with the human resources department and supervisor at his place of work. The results of the functional capacity evaluation and work capacity analysis showed that Mr. Lee would be able to resume at least part-time and light work with an ongoing work-hardening programme and vocational counselling. As Mr. Lee’s condition showed obvious improvement after the first 2 weeks, visits to the work site and discussion of return-towork issues with the human resources department of the company were arranged right away. It was crucial for Mr. Lee, the company and the therapist to discuss matters related to modified work tasks, an adapted work environment and the expectations of Mr. Lee’s returning to work to maximise the success. Intermittent work trials, with the occupational therapist as the work coach, are good practice. It is, however, important for the occupational therapist to work with the multidisciplinary team to set up a realistic return-to-work plan, particularly with regard to safety limits and precautions. By the end of the 8-week programme, Mr. Lee’s back pain was slightly lessened, but more importantly, he resumed working part-time in the restaurant, increasing to full-time employment soon after.

The Occupational Therapy Process The occupational therapy process offers a therapeutic framework to guide therapists in implementing the assessments and interventions for clients who suffer

Occupational Therapy for Chronic Pain 575

from chronic pain. Depending on the problems presented by the client, occupational therapists adopt different theories for conceptualising the assessments and interventions relevant to the individual. Listed below are the most common occupational therapy processes for managing clients suffering from chronic pain where the goal is a return to work.

3.

Client assessment Assessment of the impact of chronic pain on a client’s occupational performance is crucial. Assessments cover the needs and performances required by the different life roles that the client undertakes. In general, they can be grouped under self-care, paid and unpaid work, interests and leisure pursuits, customary habits and routines, and family and social interactions. Most of the assessments used by occupational therapists involve evaluation based on objective criteria of role functions and performance competence. For instance, the work performance of a formwork carpenter who suffers from a sprained back can be measured with the VALPAR Component Work Samples and be compared with the performance criteria set out in the Dictionary of Occupational Titles (DOT) or O*NET [20, 21]. The extent to which the pain experienced by the client affects life role function can be assessed by the Canadian Occupational Performance Measure [6] and the Oswestry Disability Index [12]. There are assessments which also involve the perceived needs and performance of the client such as the Satisfaction with Performance Scaled Questionnaire [8, 41] and LLUMC Activity Sort [38]. These instruments are briefly described below: 1. VALPAR Component Work Samples (VCWS): VCWS were designed for use in the vocational evaluation field. This system connects evaluation and treatment together and becomes standard operating equipment in occupational and physical therapy contexts. There are 21 individual work samples in the VCWS series. The VCWS are criterionreferenced instruments characterised with normative information and Methods-Time Measurement (MTM). 2. Dictionary of Occupational Titles (DOT) or (O*NET): DOT or O*NET is a comprehensive database of worker attributes and job characteristics for clinicians to

4.

5.

6.

identify and develop the skills of a member of the workforce. The database provides an essential foundation for facilitating career counselling, education, employment and training activities, and contains information about knowledge, skills, abilities, interests, general work activities and work context. Canadian Occupational Performance Measure (COPM): COPM is an individualised criterion-referenced assessment tool designed for measuring changes in occupational performance of clients receiving occupational therapy through self-report and semistructured interview which mainly focuses on clients’ competence in the performance of self-care, productivity and leisure. Oswestry Disability Index (ODI): ODI, also called the Oswestry Low Back Pain Disability Questionnaire (ODQ), is a 10-item selfadministered questionnaire used to quantify the disabling effects on daily living due to low back pain. Satisfaction with Performance Scaled Questionnaire (SPSQ): SPSQ is a 46item questionnaire used to measure clients’ satisfaction with their self-perceived performance. LLUMC Activity Sort: LLUMC Activity Sort is a self-report assessment designed to evaluate the extent to which clients perceive their competence in handling household tasks through manipulating various domestic tools.

Intervention Intervention for clients is usually focused on facilitating the client’s re-engagement in his or her role. In some instances, the client may need to strike a balance between different life roles, such as those of worker and of homemaker. Occupational therapists might integrate theories and techniques developed in other fields into the occupational therapy process in order to achieve desired therapeutic effects. The most common theories are ergonomic and biomechanical [8, 30] and cognitive behavioural [24, 31, 32]. The contributions of each of these approaches to the design of an occupational therapy programme for clients suffering from chronic pain with the goal of getting the client back to work are described below.

576 Chetwyn C. H. CHAN, Connie Y. Y. SUNG

Ergonomic and Biomechanical Approach

Pain Management Unit (at Bath) developed by Shannon [30] and the pilot programme developed by Chan et al. [8] in Hong Kong. The common features of programmes using the ergonomic and biomechanical approach are listed in Table 36.01.

This approach makes use of the theories and principles developed in the ergonomic and biomechanical disciplines, with the aim of identifying and eliminating the cause of the ongoing pain and promoting functional restoration through vigorous physical reconditioning and graded activity programmes [29]. As the focus of this chapter is on adult clients, functional restoration is geared toward re-establishing the work role and specific work-related skills of these clients in order to achieve the goal of returning to work. Occupational therapists design work rehabilitation (or return-to-work) programmes, in which the clients are required to restructure their work roles and receive training on work-related skills. Such programmes may last from 2 weeks to a few months. The training process makes reference to the functional restoration programme previously developed by Mayer et al. [28], which targets the reduction of pain symptoms, rapid improvements in a range of joint movements, activity tolerance and a work-hardening programme based on the workoriented rehabilitation services developed originally by Matheson [27]. A newer approach adopts an eclectic mix of education, training, simulation and prevention, such as the INPUT programme and

Depending on the client’s life role expectations, severity of pain and other physical impairments, and the resulting disabilities, intervention programmes are developed in consultation with the multidisciplinary treatment team. Offering different areas of expertise, the treatment team is in the best position to review the prognosis of the client, recommend treatment regimes, and co-ordinate the various generic and specialised intervention programmes offered to the client. The occupational therapist plays an important role in maximising the capability potentials of the client, providing a goal-directed work rehabilitation programe for the client and at the same time reinforcing the gains from the pain management programmes offered by practitioners in other disciplines, such as doctors and physiotherapists.

Table 36.01 Common features of interventions adopting an ergonomic and biomechanical approach • Movement to control pain • Exercise to correct posture and improve strength • Standing, sitting, and sleeping postures • Bending, lifting and reaching strategies • Biofeedback • Body mechanics integrated into work- related practice and training • Work-related assessment and hardening • Work simplification • Assistive devices and adaptive equipment

A typical work rehabilitation programme commences with a review of the client’s life roles (particularly the work role) and an evaluation of the skills required for performing these roles. The evaluation of work skills can take many forms, ranging from gathering information from the client and his or her employer, to surveying the work processes and demands at the worksite, to conducting a work capacity evaluation for the client [7]. The assessment may be based on common clinical instruments, such as a hand grip dynamometer, and work simulation equipment, such as the Baltimore Therapeutic Equipment (BTE) Primus and the VALPAR Component Work Samples [22]. Depending on the specific conditions of the client, the goal of such intervention can vary from training to return to the original job position and company, and training to return to the original company but for a different job position (usually a lighter or less demanding job), to training to engage in a different job in a new company, and training to engage in unpaid work such as volunteering or helping with domestic chores at home. The main differences in the interventions of all these return-to-work options are found in the criteria concerning what the client is expected to achieve by the end of the programme. In general, returning to the original

Occupational Therapy for Chronic Pain 577

job position and company is the most demanding and challenging for the client, whereas engaging in unpaid work is the least so.

Cognitive Behavioural Approach

The main characteristics of the intervention programmes which use the ergonomic and biomechanical approach are that the goals and training media are underpinned by these principles. For instance, for clients with back pain, classes on body mechanics, energy conservation and work simplification are usually provided at the beginning of the programme [30]. The reason for incorporating an educational component in the intervention programme is to facilitate the development of positive attitudes towards back protection and injury prevention during the training and, more importantly, at the workplace after the client’s return to work. Education may also include oneto-one coaching on the adoption of correct posture and body mechanics. There are, in fact, training programmes which use the biofeedback technique to facilitate learning of posture adjustment and movement patterns while performing work-related activities [30].

The approach taken for managing chronic pain is not designed to cure the pain but to train clients to live with the pain while leading a productive life. The cognitive behavioural approach is commonly used in occupational therapy to enable clients with chronic pain to engage in a productive life that is both feasible and acceptable to the client. In occupational therapy, the cognitive behavioural approach offers a theoretical framework for analysing the problems encountered by the clients and hence designing appropriate interventions for them. Readers who have the desire to learn about the basic assumptions and applications of cognitive behavioral therapy can consult Chapter 38 of this book or the literature [14, 33].

An individualised work reconditioning and hardening protocol is another characteristic of this intervention programme. The training protocol aims to maximise the client’s work capacity and chance of returning to work by putting the emphasis on teaching critical job factors such as the lifting and carrying functions for a shopkeeper. Graded lifting and carrying activities are simulated using VALPAR Work Samples and the BTE Primus [8]. The maximum output and average work performed across treatment sessions are monitored. The final outcome is for the client to reach a level which matches that required by the job. The main features of a work-hardening programme for clients who suffer from chronic pain is to monitor how the pain is aggravated by the training at a low level and to rely on both objective and self-perceived measures of performance [8]. A combined approach, integrating health and return to work, is beneficial for clients returning to employment or to other productive activities [18]. This approach was found to be more effective than individual- and non-return-to-work-based approaches. General pain management programmes which do not address return-to-work issues were also found to be less effective for clients who were expecting to return to employment [37].

The relevance of the cognitive behavioural approach to the practice of occupational therapy for chronic pain lies in the notion that other factors, such as the psychosocial and environmental, can be more effective than physical factors in facilitating clients with chronic pain to cope (or live) with the pain [39]. More importantly, the mechanisms of the positive effects rest on the changes in the clients’ values and attitudes toward the pain which they are still experiencing rather than the perception of the pain itself. Such changes lead to modifications in the clients’ behaviours, such that they become more active and less maladaptive, and hence more ready to re-engage in their expected life roles [1, 17, 26, 34]. Based on the cognitive behavioural approach, occupational therapists use different strategies when working with clients. Individual or group sessions are conducted, depending on the needs of the client and the aims of the intervention process. Strategies may include general medical knowledge on maladaptive behaviours due to chronic pain, such as avoidance of physical activity, anxiety and stress arising from pain and disability, and interventions, such as self-instruction, goal setting, relaxation, positive coping with pain, assertiveness training and imagery training [11, 25, 33]. The common strategies used by occupational therapists for dealing with clients with chronic pain are listed in Table 36.02.

578 Chetwyn C. H. CHAN, Connie Y. Y. SUNG

Table 36.02 Common strategies used with the cognitive behavioural approach to chronic pain • Psycho-education • Setting short- and long-term goals • Developing a daily routine • Pacing of activities • Coping strategies and appraisals • Distraction • Relaxation • Visual imagery • Positive thinking • Play and art • Use of meaningful occupations/activities.

development of treatment goals and the exploration of vocational options. In the second week, the clients participated in a training programme of generic skills such as pain management, relaxation, and building of physical and mental efficacy. In the third week, the clients were engaged in preparatory sessions on psychosocial and work adjustment and job interviews. The results of the clinically controlled trial conducted by Li et al. [24] indicated that the 3week programme was able to significantly improve the clients’ work readiness, level of anxiety and self perceived health status, as measured by the Short Form Health Survey (SF-36). Control of the negative emotions associated with chronic pain, such as pain level, motivation and anxiety level, significantly decreased. It was concluded that the return-to-work programme improved injured workers’ motivation and employment readiness [24].

Conclusion Previous studies have indicated that group-based intervention is useful for encouraging clients with chronic pain to re-engage in a work role. For instance, Arutaa et al. [2] and LeFort et al. [23] both reported that changes in the pain coping and stress management behaviours of injured workers were found to increase the workers’ readiness to return to work. These studies further revealed that the workers were able to cope with the pain in their life and work, which subsequently improved their quality of life. In a recent study, Li et al. [24] designed a 3-week training programme for workers suffering from chronic pain who had failed to return to their preinjury job and employer. The cognitive behavioural approach was used to structure the intervention process and content of the training programme. For instance, in the first week, the clients received individual counselling which targeted the reestablishment of expectations and life roles, the

The occupational therapist is an integral member of the multidisciplinary team treating clients with chronic pain. For these clients, the aim of intervention is not to eliminate their pain but rather to maximise their potential because they will inevitably experience differing levels of residual pain. This potential will enable the clients to reengage with their identified life goals. Aside from the occupational therapy process, which offers a framework for structuring the intervention, the occupational therapist will adopt different theoretical models to best explain the patients’ maladaptive behaviours, attitudes and thinking, and prognosis. These models can be used in isolation or in an eclectic way to help the therapist construct specific programmes for assisting the clients in the achievement of their set goals. For adult clients with chronic pain, resuming a productive role and returning to work appear to be the most relevant aims in modern societies.

References 1. 2.

Adams JH, Williams AC. What affects return to work for graduates of a pain management program with chronic upper limb pain? J Occup Rehabil 2003;13:97–106. Arutaa T, Malinchoc M, Offord KP, et al. Status of patients with chronic pain 13 years after treatment in a pain management center. Pain 1998;74:199–204.

Occupational Therapy for Chronic Pain 579

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34.

Baker P, Goodman G, Ekelman B, et al. The effectiveness of a comprehensive work hardening program as measured by lifting capacity, pain scales, and depression scores. Work 2005;24:21–31. Barkin R, Lubenouw T, Bruehl S, et al. Management of chronic pain: Part II. Dis Mon 1996;42:457–507. Carpenter L, Baker G, Tyldesley B. The use of Canadian Occupational Performance Measure as an outcome measure of a Pain Management Program. Can J Occup Ther 2001;68:16–22. Chan CCH, Lee TMC. Construct validity of the Canadian Occupational Performance Measure. Occup Ther Int 1997;4(3),229–47. Chan CCH. Introduction to the process of occupational rehabilitation. In Chan CCH, Hui KYL, Lo EKS, Lo SY, Kwok TWW, eds. Cumulative Trauma at Work. Hong Kong: Hong Kong Workers’ Health Centre, 2001:41–54. Chan CCH, Li-Tsang CWP, Hung LK, et al. A standardized clinical series for work-related lateral epicondylitis. J Occup Rehabil 2000;10;143–52. Chan CCH, Sanderland J, Rivard A, et al. The utility of an occupational performance model to productivity evaluation. Hong Kong Journal of Occupational Therapy 1998;9:3–9. Cheng JCK, Li-Tsang CWP. A comparison of self-perceived physical and psycho-social worker profiles of people with direct work injury, chronic low back pain, and cumulative trauma. Work 2005;25:315–23. Cheung YL, Molassiotis A, Chang AM. A pilot study on the effect of progressive muscle relaxation training of patients after stoma surgery. Eur J Cancer Care 2001;10:107–14. Chow JHW, Chan CCH. Validation of the Chinese version of the Oswestry Disability Index. Work 2005;25:307–14. Fisher K, Johnston M. Emotional distress and control cognitions as mediators of the impact of chronic pain on disability. Br J Health Psychol 1998;3:225–36. Fordyce WE. Behavioural Methods for Chronic Pain and Illness. St Louis, MO: CV Mosby, 1976. Gatchel RJ, Mayer TG, Hazard RG, et al. Editorial: Functional restoration. Pitfalls in evaluating efficacy. Spine 1992;17:988–95. Gatchel RJ, Turk DC, eds. Psychosocial Factors in Pain: Critical Perspective. New York: Guilford Press, 1999. Jensen MP, Romano JM, Turner JA. Patient beliefs predict patient functioning: Further support for a cognitivebehavioral model of chronic pain. Pain 1999;81:95–104. Karjalainen K, Malmivaara A, van Tulder M, et al. Multidisciplinary biopsychosocial rehabilitation for subacute low back pain in working-age adults. Spine 2001;26:262–9. Law M, Polatajko H, Baptiste S, et al. Core concepts of occupational therapy. In Townsend E, ed. Enabling Occupation: An Occupational Therapy Perspective. Ontario: Canadian Association of Occupational Therapists, 1997. Lee GKL, Chan CCH. Use of dictionary of occupational titles (DOT) on formwork carpentry: A comparison between the United States and Hong Kong. Work 2003;20:103–10. Lee GKL, Chan CCH, Hui-Chan CWY. Consistency of performance on the functional capacity assessment. Static strength and dynamic endurance. Am J Phys Med Rehab 2001a;80:189–195. Lee GKL, Chan CCH, Hui-Chan CWY. Work profile and functional capacity of formwork carpenters at construction sites. Disabil Rehabil 2001b;23:9–14. LeFort SM, DonaldKG, Rowat KM, et al. Randomized controlled trial of a community-based psycho education program for the self-management of chronic pain. Pain 1998;74:297–306. Li EJQ, Li-Tsang CWP, Lam CS, et al. The effect of a “training on work readiness” program for workers with musculoskeletal injuries: A randomized control trial (RCT) study. J Occup Rehabil 2006;16:529–41. Linton SJ. A review of psychological risk factors in back and neck pain. Spine 2000;25:1148–56. Marhold C, Linton SJ, Melin LA. Cognitive-behavioral return-to-work program: Effects on pain patients with a history of long-term versus short-term sick leave. Pain 2001;91:155–63. Matheson LN. Work Capacity Evaluation: Interdisciplinary Approach to Industrial Rehabilitation. Anaheim, CA: Employment and Rehabilitation Institute of California, 1984. Mayer TG, Gatchel RJ, Mayer H, et al. A prospective two-year study of functional restoration in industrial low back injury. An objective assessment procedure. JAMA 1987;258:1763–7. Rosomoff HL, Rosomoff RS. Comprehensive multidisciplinary pain center approach to the treatment of low back pain. Neurosurg Clin N Am 1991;2:877–90. Shannon E. Reflections on clinical practice by occupational therapists working in multidisciplinary pain management programmes in the UK and the USA. Aust Occup Therap J 2002;49:48–52. Spence SH. Cognitive-behavior therapy in the management of chronic, occupational pain of the upper limbs. Behav Res Ther 1989;27:435–46. Spence SH. Cognitive-behavior therapy in the treatment of chronic, occupational pain of the upper limbs: A 2-year follow-up. Behav Res Ther 1991;29:503–9. Turk DC, Meichenbaum D, Genest M. Pain and Behavioural Medicine: A Cognitive-Behavioural Perspective. New York: Guilford Press, 1983. van Tulder MW, Ostelo R, Vlaeyen JWS, et al. Behavioral treatment for chronic low back pain, a systematic review within the framework of the Cochrane back review group. Spine 2000;26:270–81.

580 Chetwyn C. H. CHAN, Connie Y. Y. SUNG

35. Vlaeyen JWS, Linton SJ. Fear-avoidance and its consequences in chronic musculoskeletal pain: A state of the art. Pain 2000;85:317–32. 36. Waddell G. Low back pain: A twentieth century health care enigma. Spine 1996;2:2820–5. 37. Watson PJ, Booker CK, Moores L, et al. Returning the chronically unemployed with low back pain to employment. Eur J Pain 2004;8:359–69. 38. West Evaluation Systems Technology. LLUMC Activity Sort. Long Beach, CA, 1986. 39. Wittink H, Hoskins Michels T. Chronic Pain Management for Physical Therapists. Boston: Butterworth-Heinemann, 1997. 40. Wressle E, Samuelsson K, Henriksson C. Responsiveness of the Swedish version of the Canadian Occupational Performance Measure. Scand J Occup Ther 1999;6:84–9. 41. Yerxa EJ, Burnett-Beaulieu S, Stocking S, et al. Development of the Satisfaction with Performance Scaled Questionnaire (SPSQ). Am J Occup Ther 1988;42:215–21. 42. Young A, Russell J. Demographic, psychometric, and case progression information as predictors of return to work in teachers undergoing occupational rehabilitation. J Occup Rehabil 1995;5:219–34.

37

Peter W.H. LEE, Amy S.M. FUNG

Psychological Management in Chronic Pain

INTRODUCTION CHRONIC PATIENTS IN REAL LIFE Case A: Complaint of unremitting back pain in a former construction worker Case B: Psychopathological consequences of a crush injury in the right hand of a carpenter Case C: Chronic pain disability complicated by personal injury claims STRATEGIES FOR ASSESSMENT AND TREATMENT Early diagnosis and intervention Non-organic factors Longitudinal over cross-sectional perspectives Going beyond traditional diagnosis Case specificity CURRENT UNDERSTANDINGS AND TREATMENT IMPLICATIONS Fear-avoidance Depressed mood Acceptance Positive versus negative affect Personality and other psychiatric morbidities

Introduction Chronic pain has a profound impact on the sufferer’s life. Robinson et al. noted, that “many chronic pain patients develop co-morbid depression; they utilise medical care excessively and feel wronged by the care they receive; many leave their jobs; obtain disability and settle into a lifestyle that, at best, bears faint resemblance to that they once imagined were possible” [44]. The “complex set of physical and psychosocial burden” of chronic pain patients including: immobility and consequent wasting of muscle and joints; depression of the immune system and increased susceptibility to disease; disturbed sleep; poor appetite and nutrition; dependence on medication; over-dependence on family and other caregivers; overuse and inappropriate use of professional health care systems; poor job performance or inability to work; disability; isolation from society and family, turning inwards; and anxiety, fear, bitterness, frustration, depression and suicide was highlighted by Niv and Devor [38]. This chapter aims to provide a review of the psychological considerations relevant to the clinical understanding and management of chronic pain. Comprehensive assessment is emphasised, for without an adequate understanding of the underlying problems effective treatment cannot be achieved. With better understanding, realistic goals can be tailored to the unique condition of each individual patient. Management of chronic pain, however, is a science (demanding professional and technical expertise) — and an art (requiring skilful delivery and application of professional knowledge). The foundation for effective assessment and realistic goal setting depends crucially on

582 Peter W.H. LEE, Amy S.M. FUNG

the important collaborative patient-clinician relationship, with great demands on the interpersonal skills of the clinician.

Chronic Pain Patients in “Real Life” Chronic pain may be described in terms of location, duration, intensity and presence or absence of verifiable physical underpinnings. However, the essential features of chronic pain, including the characteristics and vulnerability of the person afflicted; aetiological, aggravating and maintaining factors; idiosyncratic responses to the pain sensation, threat and/or meaning assigned to pain; impact on quality of life; resultant impairment and distress of the person afflicted, simply defy any easy conceptualisation. Three cases are presented here to illustrate the complexity, and the diverse sources and pathways of influence, of the characteristics of patients with chronic pain. Points of clinical relevance are noted within brackets.

Case A: Complaint of unremitting back pain in a former construction worker

Anger and neuroticism Litigation Workplace related factors GUIDELINES FOR PSYCHOLOGICAL INTERVENTIONS SUMMARY AND CONCLUSION REFERENCES

Mr. A was a 42-year-old male who had not worked for 2 years after sustaining a back injury. He claimed that repeated courses of physiotherapy were “not useful at all”. He had had multiple magnetic resonance imaging investigations, which indicated mild posterior bulging of the L4/5 intervertebral disc with no dural-sac or nerve-root compression. However, according to the patient, some doctors had told him he was alright but other doctors had told him otherwise (viz. iatrogenic influences due to conflicting medical advice). The patient had no clear idea of what was wrong. He had been diligent in exercising to strengthen his back “as instructed by the physiotherapist”. However, this had resulted in aggravation of the pain. He became “very disappointed” that he had to put up with multiple “inconveniences” in his everyday life (viz. issues with expectations and non-acceptance). He resented the doctor telling him “nothing further can be done” except to “just” give him analgesic medication, but who also warned him he had to choose whether or not to put up with the side effects of this on his stomach (viz. perceived doctor’s unhelpfulness may aggravate adverse reactions). He complained bitterly of pains of a constant nature throughout the day (viz. attentional factors leading to fixation on pain). He had “non-stop” discomfort and sensations of tightness at the back of his neck, and pains and numbness extending from the upper to the lower back, and down the back of both legs.

Psychological Management in Chronic Pain 583

In terms of personal and family background, he had a distant relationship with family members. He had received junior secondary education and started work at the early age of 15. He had taken up various trades, having worked as an apprentice hairstylist and then a driver of goods vehicles. He subsequently started his own transportation business, and made a good profit initially. He took pride in having once owned two heavy trucks at the peak of his success. However, the “economy turned bad” and he incurred heavy financial losses. He closed his business and resumed work as a cranelorry driver in construction sites (viz. prior history of failures and strain may serve as a vulnerability factor). He married at 31, but divorced 5 years later. He had two sons aged 10 and 8, who lived with their mother with whom he had minimal contact. He later cohabited with his girlfriend and had “some good times”. However, she left him when he had no money to support her extravagant spending. She also resented his bad temper — he hit her when they argued (viz. secondary losses: pain leading to frustration, lowered self-esteem, irritability and negative mood, further aggravating the problem). At the time of psychological consultation, he was living on his own. His only social contact was the occasional visit of one of his sisters (viz. social isolation and loss of previous lifestyle). Mr. A’s daily routine consisted of getting up at “10 or 11 am or even noon”. He wandered about in the neighbourhood. He read newspapers at home, watched TV, listened to radio or music, or played a disc to watch a movie. He had a lunch box at midday, and cooked a simple meal for dinner. He watched TV in the evening and retired to bed at 11 pm (viz. reinforcing nature of a listless and non-productive lifestyle). He felt he could not work again (viz. disuse syndrome, atrophy of skills and physical stamina, leading to further loss of confidence and inertia, development of a career of chronic pain). He had not met with friends for a long time because he had no money to spend (viz. social isolation). He admitted to being hot tempered with a low frustration tolerance and he tended to be critical and argumentative when with friends (viz. pain having an adverse impact on mood). He said he had little interest in interacting with others and had no morale and no fighting spirit (viz. diminished interest characteristic of depressed mood). He was in debt. He saw a dismal

future ahead, and anticipated having great difficulty getting back into a trade “being not old but not young” (viz. market and reality factors).

Comments This case highlights the progressive and snowballing impact of chronic pain. Poor understanding and inadequate medical explanation led to continuing concerns and fears as pain persisted. Felt pain is accentuated by attentional fixation, leading to increased signal value of even minor noxious physical sensations. Habitual life functions are impaired as behavioural avoidance and a listless daily routine become entrenched. In Mr. A’s case, being poorly informed of his back condition and having little trust in doctors led to a chronic sense of dread and danger associated with any pain sensation. “Not knowing” what is wrong can be scary and unsettling, and serves to maintain an undue vigilance on symptoms. Protective behaviours and progressive restriction of daily life activities are almost inevitable, leading to failure to return to work. Individuals who have been previously physically active may be more adversely affected, given the tendency to compare their current (unsatisfactory) condition with past physical prowess. Such individuals have difficulty accepting that a symptom experienced now but not previously experienced may be benign and not a sign of progressive or serious physical pathology. Individuals who strongly identify with physical strength may also have difficulty accepting the human impact of normal ageing with certain wear and tear. After injury, previously unnoticed symptoms (e.g. musculoskeletal) of normal ageing or overuse may be amplified and acutely perceived with concern and alarm. In chronic pain conditions, an overwhelming task that has to be tackled is that of dealing with loss of functional abilities. The Committee on Handicaps Group for the Advancement of Psychiatry in their report [11] cautioned that “each individual must build a new identity and a new way of dealing with the world. The process of working through these issues cannot be rushed but must occur in an individualised mix of stimulus and reward, small success and failure”. Preservation of self-esteem through continued activity and skills adaptation is needed. Mr. A, being used to physical exertion, had obvious difficulties coming to terms with his impaired physical functioning after his injury. Not used

584 Peter W.H. LEE, Amy S.M. FUNG

to a diminished role and a daily listless routine, he periodically acted out his frustration through temper outbursts. Unfortunately, this led on to social isolation and more life difficulties (departure of his girlfriend, distancing of friends) which further undermined his self-esteem. Mr. A’s temper outbursts and intolerance of his life condition after injury may represent “the last straw” in a chain of tough life conditions he had endured for years, from hard work since an early age, disappointment and financial losses due to business failure, and culminating in poor acceptance of having to work as an employee (instead of being an employer himself ). The workplace may also have been perceived as being physically demanding and a potential source of further threat and re-injury. Returning to the workplace with diminished physical abilities may have posed a serious threat to his self-esteem, especially in having to put up a brave front and “face” up to co-workers while being uncertain of their reaction. With extended sick leave and time away from work, progressive social isolation, loss of a productive daily life routine, diffidence and low self-esteem, unremitting felt pain served as a convenient reason for not returning to work. Treatments geared solely towards physical strengthening and pain reduction logically thus proved to be of “little use”, as once chronicity has set in, more potent aggravating and maintaining factors have come into play to influence the clinical picture. The unsatisfactory efficacy of traditional treatments for chronic pain has been well reported. Boersma and Linton noted in their study on chronic pain patients that despite having “fair to moderate amounts” of health care focused on pain and function, at the end of a 7-month study period, the patients’ function did not improve and neither did the rate of sick leave [6]. Without a clear understanding of the complexity of the chronic pain problem, the patient and the clinician may both become stuck in defining all problems as simply pain problems. Eccleston and Crombez rightly noted that “rigidity in problem definition may lead to yet more problems of distress and disability” [14]. Loeser cautioned that “People have diseases, not tissues or organs. Illness is the interaction of the disease with the world of the patient, and pain can certainly lead to illness. Examining a damaged nerve does not tell us whether or not the disease of chronic pain is present. Pain as a disease is resident

only in the entire person, not his or her parts… only an entire person can harbor a disease” [29]. Effective rehabilitation of patients with chronic pain problems, such as presented by Mr. A, has to incorporate multiple treatment components including better education, understanding and acceptance of the static yet non-progressive nature of the felt pain; desensitisation towards mild noxious sensations to make way for better functions and gainful resumption of work; restoration of faith, confidence and self-esteem; enhancement of motivation; and a value reorientation in favour of a productive working life over an invalid chronic pain career. Actions, rather than talk, however small to begin with, are essential for reversing the negative spiral towards intractable disability and misery.

Case B: Psychopathological consequences of a crush injury in the right hand of a carpenter Mr. B, aged 55, was born into a fishing family. He enjoyed a good relationship with his siblings. He had been educated up to Primary 4 and had assisted his parents in fishing since his early teens. He later took up carpentry work. He adjusted well to work and enjoyed a good relationship with his colleagues. He regarded himself as a responsible worker who was always eager to take on “any hard work”. He was happily married with three children. He and his wife enjoyed common leisure activities including window-shopping, having tea and dim sum in restaurants, karaoke, and playing mah-jong. He enjoyed general good health prior to his injury. He was also an enthusiastic practitioner of Chinese martial arts. He reported “stupidly” injuring his right hand — i.e. an accident that should not have occurred, (viz. psychological meaning of injury site) when someone slammed a door shut, catching the back of his hand. He said a “huge chunk” of flesh had been ripped open and he had intense pain which felt like “nails hammered into my hand”. He felt dizzy and nearly passed out. Under general anaesthesia, his wound was sutured with “29 stitches”. He attended a health clinic daily to clean his wound. Despite taking analgesics, he had constant and intense pain which disrupted his sleep. He ruminated on why he should be “so stupid” to get injured like this. He became irritable and

Psychological Management in Chronic Pain 585

agitated. Over the next month or so, he was at times so much bothered by the “intense and incessant” pain that he had considered “solving” it all by jumping off the roof (viz. depressed mood triggered by injury and pain). He was angry that he “could not do anything” (viz. phenomenon of spread and self-devaluation). He could not brush his teeth, eat properly or shower. He felt useless. He was “tormented” by pain, helplessness and a depressed mood, particularly as the injury was “so unnecessary”. In the daytime, he was alone at home as his wife and children went out to work. He brooded on negative thoughts and remained agitated as his pain proved non-responsive to treatment. Such prolonged recovery was “just not anticipated”. Mr. B suffered severe soft tissue damage due to a crush injury of the right hand. A deep palm laceration with a contused ulnar nerve was noted. He had persistent pain over the right hypothenar eminence, and middle and ring fingers with numbness, weakness, and swelling; decreased sensation over the right C5, 6, 7 and 8 dermatomes; and weakness of the right elbow, wrist, and finger flexion and extension. Complex regional pain syndrome was diagnosed. Despite prolonged courses of conservative treatments, the numbness and discomfort remained. He was “routinely” woken up by a prickling and stinging sensation between about 1 and 2 am and could not get back to sleep. In the night, he was intensely distraught and felt like “shouting out loud”. He became increasingly helpless despite trying “incessantly” to think of ways to lessen the pain and discomfort (viz. attentional fixation on pain and distress). He was very unhappy with the weakness in his right hand and the resultant multiple inconveniences in everyday life. He could no longer practise his kung fu. He tried to resume work, but after an hour or so, he had “intense” aggravation of the pain. He became more convinced of the “sinister” nature of his pain and became preoccupied with worries concerning further aggravation and deterioration (viz. catastrophic thinking). He quit his job. His daily routine, however, was reported as “satisfactory”. He went for an early morning walk between about 4 and 5 am; sat about and relaxed, and did gentle exercises. He read the newspapers and listened to the radio. He had lunch in a local cafeteria.

His appetite was fair. In the afternoon, he went window-shopping or read magazines in a library. He returned home in late afternoon, sat about, watched TV, read newspapers and waited for his wife to return from work. Dinner was cooked by his wife. They chatted and watched TV together. He retired to bed at 10 pm. He felt his daily life was “OK”, as long as he did not think about his pain and future. However, as it dawned on him that his pain was likely to remain, he became very downcast, agitated and angry. He had recurrent suicidal thoughts and considered “choosing” not to burden himself or anyone anymore. At times, he portended worsening of his condition and blamed his bad luck. He could not accept the possibility of being afflicted with any degree of pain, however minor, for the rest of his life (viz. an inflexible and perfectionistic attitude). He also had worries concerning finances, the outstanding mortgage, his wife becoming unemployed and his not ever being able to resume work. He often experienced a “sinking feeling” in his heart. He felt sad as he anticipated a “painful life and future” which was drastically different from the life he had previously had or hoped for. Despite maintaining a satisfactory relationship with his wife, his sexual life “deteriorated significantly”. He had to exercise utmost care not to hurt his right hand during sex, but felt a man should adopt the dominant role. While his interest in sex remained, he could not maintain an erection as he was preoccupied in protecting his hand from further hurt (viz. secondary problems and handicap due to psychological reasons). He also felt his children and wife were becoming emotionally distant. He was aware of but could not control his temper and impatience over even minor frustrations (viz. depressed mood and secondary handicaps). He avoided pain by not using his affected hand. He developed a pattern where he had to be helped even in minor chores, e.g. opening a bottle, wringing a towel dry, or getting food. He could not handle chopsticks well (viz. disuse and increasing handicap). Instead, he held his chopsticks with his left hand, but felt agitated with his poor coordination. While he took on some household chores, he allowed himself to do only light work, e.g. sweeping the floor, or folding clothes. He avoided using his right hand. He felt useless and handicapped, but did not have “the courage” to use his hand more.

586 Peter W.H. LEE, Amy S.M. FUNG

Comments Mr. B’s condition is a typical demonstration of the multifarious factors which can potentially shape the course of chronic pain after acute trauma or injury. His injury and pain started from a seemingly “stupid” accident. The subsequent chronic course of the disorder illustrated how psychopathological factors beyond the original injury could complicate the clinical picture and exert an increasingly devastating influence if not promptly dealt with. Psychological significance is often attached to the site of injury. The hand, especially for man, is the key medium of contact with the outside world. The right hand, in particular, is valued as a source of power and influence. Injury and loss of functions of the right hand is a major loss in many respects. The psychological consequence of right hand injury is amplified as there is no way of hiding the “diminished” organ. In Mr. B’s case, he was also very unforgiving of himself for being involved in a “stupid” accident with such longlasting implications. He just could not get over the nature of his accident and became continually obsessed with his “stupidity” and “bad luck”. Mr. B reacted with intense dread not only to his pain, but also to the possibility of re-injury and further loss of function of his right hand. The psychological phenomenon of “spread” and “devaluation” is a relevant consideration here. For vulnerable individuals, disability and pain in a specific site may “spread” and extend to encompass a subjective sense of devaluation of the entire person. Mr. B suffered a significant loss of self-confidence and esteem due to pain, inertia and indeed voluntary “abdication” in using his right hand. A recent note on “mental defeat” in chronic pain which echoed the original concept of spread and devaluation was proposed by Tang et al. [51]. Ehlers et al. [16] noted that mental defeat represented “the perceived loss of autonomy in the face of uncontrollable traumatic events, resulting in the person giving up efforts to retain identity and self-will”. In Mr. B’s case, demoralisation and sense of loss of personal control aggravated and maintained his fixation on pain. His growing demoralisation was seemingly untouched by even an “OK” daily life routine. The “okayness”, unfortunately was segregated from his core personal identity as his unremitting pain continued to rob him of his sense of control and competence. Mr. B’s chronic pain fixation was

also maintained by his inflexibility and inability to accept some loss or diminution in function, and this served to block awareness and deployment of other intact functions. With chronicity setting in, Mr. B had likely also become complacent with a non-productive daily routine. While not necessarily conscious of it, the secondary gains of having more assistance and attention from family members served to vindicate and compensate him for the long years of hard work and sacrifice he had provided the family. Non-return to work also served to reduce his worries about stigmatisation and allowed escape from potential social rejection, further threats of incompetence and further injuries. The impaired role with its many socially sanctioned advantages can quickly become addictive and present additional hurdles in rehabilitation.

Case C: Chronic pain disability complicated by personal injury claims Ms. C reportedly was injured in two work-related incidents. She saw many doctors and attended 4 years of outpatient treatment with no demonstrable improvement. At the time of attending for psychological consultation, she was suing for personal injury compensation. Ms. C worked as an attendant in a home for mentally retarded adults. The first accident happened when she was helping a “too fat” resident in the toilet. The resident was clumsy, began swaying and started to fall backwards. Ms. C instinctively held out her hand. The resident grabbed her left thumb, but eventually fell to the floor. Initially, Ms. C felt no pain. However, later in the evening, her left hand and forearm felt like “fire burning”, as if her thumb had been “chopped off” or “torn off forcibly”. She also complained of sensations of being “stabbed” in the left upper chest and back. The pain intensity was rated as 9 on a scale of 0–10 (10 being most severe, an unbearable pain). She had burning sensations when her hand touched “anything”, however lightly. She reported being “like a robot” and could not turn her entire body. She could not move her shoulders. She could not move her thumb. At the end of 1 year of sick leave, her doctor recommended that she resume work, but that

Psychological Management in Chronic Pain 587

she should “not try too hard”. She returned to work and was spared physically demanding tasks. She had “persistent but bearable” pain. She was convinced that “things broken would for ever leave a mark even after repair”. On the third day of work, while assisting a colleague with a resident in the bathroom, the woman had an epileptic fit and began to fall. Her colleague supported the resident as best she could. Ms. C also tried to help, but lost her balance and ended on the floor, tearing her trousers. She felt “nothing unusual” afterwards. However, she woke early the next morning with an intense numbness extending from her small finger across the entire right palm. She sought treatment at a hospital accident and emergency department. On reviewing her case notes, the doctor commented, “You’ve already taken 1 year of leave, and you want to try again?” The doctor reportedly did not examine her and told her she was “alright”. She was given analgesic medication and 1 day’s sick leave. She resented the doctor’s treatment.

was emphatic that she had no psychological distress of any nature.

Subsequently, Ms. C complained of unremitting “pain till death” with tightening sensations on the right neck, stretching and cramping sensations over the entire right side of her body, and pain and tension from the buttock up her back. She also had numbing sensations “24 hours a day” (viz. emotionally laden descriptions which are incompatible with clinical reality). She could not move and rested at home. She resumed work on the second and third days. However, after sweeping the floor she had “extreme exhaustion” and “tearing” sensations in her neck and back.

At assessment, Ms. C was neat and smartly dressed. She looked well despite walking with an awkward limp. She was not anxious, depressed, or overtly distressed.

She saw doctor after doctor and never resumed work again. When seen for psychological assessment, Ms. C complained of constant pain of an intensity of 4–5, coupled with unpredictable aggravations of excruciating pain reaching an intensity of 10. She had neck pain when she raised her head, unremitting pains in the middle of her back and right buttock, and pains on the back of the right thigh and left sole. She repeated several times her doctor’s comments that she had to be “prepared to have pain for the rest of her life”. Despite having pain “all the time”, Ms. C reported having a calm and placid mood. Her mood was allegedly unaffected by pain or impairment. She

Ms. C asserted that she pursued litigation “not for money” but to redress her sense of “unfairness”. She felt bitter that despite being “very diligent” in obeying her doctors’ advice, they doubted her trustworthiness. She resented being ignored by doctors despite her “obvious swellings and pains”. She resented being slighted by doctors even before having “any” investigation and/or examination. She held an intense grudge towards a doctor who “threatened” her to “either” go back to work or have surgery. She resented being told her pain was “psychological” (viz. doctorpatient communication). She also felt her seniors persecuted her when they insisted she had to bring original copies of her sick-leave certificate to the office in person despite that she was in great pain. She resented her employer’s trying to dismiss her from her job.

She periodically massaged her right thigh using strong pressure with her right hand and fingers (which were supposed to be weak and in pain). She stood up from time to time to turn and stretch her body, showing no signs of pain, discomfort, agony, or emotional distress. She rested her right hand and elbow on her lap with fingers clasped into a fist showing conspicuously general weakness and disinclination for any movements (except when she massaged her right thigh). When carried away with her complaints, she could, however, reach freely behind her back for her handbag with both or either hand showing no distress. She had free and easy movements of both hands and fingers when she flipped through various legal documents. She seemed at times unsure of the location of her pains and had to feel her body to confirm the exact pain location (viz. importance of behavioural observations assessing the compatibility of demonstrated functions with subjective complaints). Mental state examination indicated that Ms. C had a good recall of her personal history. She provided a very detailed account of her injury, treatments and “unhappy” interactions with doctors, therapists and her employer.

588 Peter W.H. LEE, Amy S.M. FUNG

She was born in Hong Kong and was the eldest of six children. She now had infrequent contact with her family. Her father had indulged in gambling and neglected the family. Her mother had raised loans to support the children’s school fees. At the young age of 11, she decided to “sacrifice” herself, left school and started work. She had worked in a factory, as a seamstress, sales lady, restaurant cashier, receptionist in a doctor’s clinic, real estate agent and foreign exchange dealer. She had once earned “a lot of money”, with a monthly salary of over HK$60,000. However, she had also lost “a lot of money” through “wrongful” investments. She regarded her life as being “too loud, too hectic and too rotten” with erratic sleep and eating patterns. Although she frequented bars with colleagues, she had no “real friends”. She finally became disillusioned with her lifestyle, quit her job and enrolled in a course on Buddhism. She wished to focus on “the present” and practise Buddhist teachings. She wished to help people find meaning in life. She thus applied to work as a care home attendant with a welfare agency. She was single and reckoned she had had only one serious relationship. She had started dating her boyfriend at 16 despite her parents’ objections. They had been planning marriage when she was 27, at which point she discovered that he was already cohabiting with another woman. She blamed herself for being cheated as she had “not carried eyes to know people”. She had not dated since. She had enjoyed general good health. She had been admitted to hospital 10 years previously for “dizzy attacks” and tiredness after working and not sleeping for two days. She did not have other chronic ailments and had never sought mental health treatment.

Comments Ms. C’s complaints were highly dubious. Marked incongruity between her complaints of intense pain and the apparent lack of signs of distress were noted. Despite reporting otherwise, she was capable of a full range of movements with relative ease. She reported an incredible and extensive range of symptoms. It was highly unusual also that despite her alleged pains, Ms. C insisted her mood was not disturbed. It was rare indeed for any patient with Ms. C’s alleged intense and pervasive afflictions not

to have at least a degree of anxiety, distress, worries or negative thoughts. Ms. C’s personal injury claims went to court and the trial judge made a very succinct list of observations. The judge acknowledged that Ms. C’s condition could not be accounted for satisfactorily on the basis of known organic findings. The judge thus saw the task was one of deciding whether or not Ms. C was indeed suffering from chronic pain with a psychological and physical basis or that she was malingering — manufacturing pains and malaise which were non-existent. In view of the minor nature of the injury, the judge reasoned that it was unlikely that the alleged accidents per se could have triggered off a chronic pain disorder as the injuries lacked any features of psychological trauma. The judge finally arrived at the conclusion on the basis of a number of reasons that Ms. C was a malingerer. The reasons noted may serve as important caveats for clinicians in their understanding of chronic pain problems. Among the observations were: •

•

•

•

Inconsistencies in pain complaints. Ms. C presented different versions of pains to different doctors and therapists, and her complaints were different over different time periods. The discrepancies could not be explained by lapse of memory as they were alleged to be so severe. Faking weakness and pains during medical examinations. When Ms. C was examined for power of the upper limb by her doctors, she made little effort and contracted antagonistic muscles. The distribution of Ms. C’s complaints of diminished sensations was patchy and did not correspond to dermatomes. Surveillance video tape. Ms. C alleged that she would have “great difficulties and pain” if she tried to raise her head or hands. However, a surveillance tape of her clearly showed that while in a shop, she was able to reach up with her right hand for a product displayed on a shelf high above her head with no signs of pain. Contradictory findings in physical examinations. Muscle wastage in painful areas was absent. Despite Ms. C’s complaints of poor appetite, she had gained almost 10 kg since her injury.

Psychological Management in Chronic Pain 589

The judge further noted that while Ms. C had continued in her effort to seek treatment from various doctors, including private practitioners at her own expense, she had voluntarily taken strong pain killers over the previous 4 years despite them causing gastrointestinal upset and had also reported improvement over time. The judge also noted that Ms. C had only started seeking private treatment when doctors in the public sectors cut short her sick leave, and further reasoned that she treated her compensation-seeking exercise as an investment. In support of her claim, she had invested in consultation fees to gather medical evidence to support her case. Her reported improvement was in an attempt to persuade doctors to pursue a nonsurgical approach, enabling her to extend her sick leave while avoiding intrusive surgery.

Strategies for Assessment and Treatment Early diagnosis and intervention Chronicity begets more chronicity. The longer a pain problem drags on without resolution or relief, the more intractable it becomes. Andersson cautioned that chronicity itself is a significant negative prognostic factor [2]. For example, in low back pain patients, while 80–90% of patients may recover by 12 weeks, recovery after 12 weeks “is slow and uncertain”, and by 2 years of absence from work, the return to work rate is “close to zero”. Early diagnosis of the underlying psychopathological factors is highly recommended.

Non-organic factors Non-organic factors have been suggested to be better predictors of return to work than organic factors in chronic low back pain patients (Lancourt et al.) [27]. Important predictors include the work environment, psychosocial factors and duration of the current episode. In addition, the patient’s perception of fault, involvement of lawyers, selfprediction of disability, income, educational attainment and employer attitudes are also of prognostic significance.

Longitudinal over crosssectional perspectives: Polatin et al. studied chronic back pain patients undergoing functional restoration rehabilitation and noted that 50% showed current symptoms for at least one psychiatric disorder [41]. Of importance, however, was that 77% of the patients met a lifetime diagnosis of at least one psychiatric disorder, indicating that prior vulnerability predated and probably potentiated injury and subsequent chronicity. Common psychiatric problems noted prior to pain onset were personality disorder, depression, substance abuse and anxiety disorders. A good clinical guide is that assessment of chronic pain patients and treatment planning needs to take on a longitudinal rather than a cross-sectional focus on patients’ longstanding vulnerabilities and problems.

Going beyond traditional diagnosis A realistic assessment of chronic pain problems needs to focus “beyond diagnosis”. Loeser echoed this view and noted that “Pain as a disease is resident only in the entire person, not his or her parts… Only an entire person can harbor a disease” [29]. Instead of relying on pathophysiological and/or psychiatric diagnosis, clinicians have to understand the whole person and his/her life circumstances in order to be able to modify the underlying psychological mechanisms maintaining or aggravating the chronic pain problem. Assessment beyond diagnosis should comprise the following: • • • • •

Structural and physical pathology diagnosis to considering the whole person being affected Current psychiatric difficulties to lifetime psychiatric and psychological problems Psychiatric disabilities to prior personality problems and behavioural anomalies Patient’s complaints of pain to their perception of the significance and meaning of pain The simple motivation of pain alleviation to emotional management, fulfilment, and improvement of other life, work and relationship difficulties

590 Peter W.H. LEE, Amy S.M. FUNG

• •

•

The nature of injury to the patient’s perception of who’s at fault and degree of blame and grudge The patient’s demographic and personal characteristics to important psychosocial influences, e.g. sick role, compensation, involvement of lawyers and biased “hired gun experts”, family members’ rejection or support, litigation and compensation Current presentation to history, chronicity and factors leading to secondary handicaps, e.g. disuse, change of lifestyle, accumulation of negative life events and growing chronicity.

Case specificity The three cases highlighted illustrate the complexity and uniqueness of each chronic pain patient’s situation. Chronic pain clinicians need to familiarise themselves with theoretical formulations on possible psychological mechanisms and processes associated with chronicity so that clinical assessments and treatments may be systematically guided.

Current Understandings and Treatment Implications Key current concepts and findings implicated in effective chronic pain management are reviewed and summarised below.

Fear-avoidance Lethem et al. noted discordance between the severity of physical injury and subsequent pain complaints in some pain patients [28]. Cognitive and behavioural factors are deemed as important in influencing the chain of events linking pain experience to disability and chronicity. Catastrophic thinking associated with the pain experience, with consequent fear, avoidance, hypervigilance and over-guardedness has been reported (Vlaeyen et al.; Waddell et al.) [56, 57]. Avoidance of activity, prompted by fear (e.g. of pain, aggravation of physical condition or re-injury) and misunderstanding (Goubert) [21] lead on to further withdrawal, more generalised disuse and chronicity. Avoidance of activities serves to maintain fear of pain and/or re-injury by preventing disconfirmation that activity will lead to further harm (Turk et al.)

[54]. Avoidance of activities, once initiated, can be difficult to reverse due to the short-term effects of reduced suffering and temporary sense of security. Avoidance also prevents alleviation of unnecessarily inflated fears due to loss of opportunity to test out actual physical capacity and endurance.

Depressed mood Depressed mood is a complicating factor in chronic pain. Lack of pleasurable experiences after pain sets in, with reduced quality of daily living, together with rigidity and non-acceptance of some loss of function, increases the likelihood of negative emotions and mood disorders, and further aggravates the original problem (Romano) [46]. In a study on patients with musculoskeletal pain problems, Boersma noted that subjects with high depressive scores had the highest percentage of health care usage, yet reported the least improvement at follow-up [6]. Early assessment and intervention of depressed mood is important to prevent chronicity.

Acceptance McCracken noted that pain, being unwanted, demands attention, disrupts ongoing functions and prompts pain motivated behaviours [34]. Proliferation of pain motivated behaviours changes the patient’s life and promotes chronicity. McCracken thus argued that it may be useful to deal with the “behaviours pain occasions”. Nicholas et al. noted that activity engagement despite pain predicts better emotional adjustment [37]. Recent developments in psychological treatment have thus focused on cultivating a “purposeful allowance of pain into attention” while maintaining ongoing work and daily functions as a way of managing chronic pain. Promotion of acceptance was aimed to disrupt the adverse influence of chronic pain, reduce emotional distress, and allow for better physical and social functioning (McCracken et al.) [34]. Acceptance includes “awareness of pain along with a continuation of desired activities and without struggling for control over the pain” (McCracken) [34]. Therapeutic interventions in promoting acceptance aim to help patients to allow awareness (instead of fighting or rejecting) of their pain experience, and then to let go of the awareness to continue with

Psychological Management in Chronic Pain 591

ongoing behaviours without bringing in pain motivated behaviours. Indeed, Blyth et al. noted that while chronic pain of significant severity was common in the community, a sizeable proportion of chronic pain subjects in the community were able to lead productive lives with little need to resort to medical services [5]. These individuals seemed to be able to achieve a high level of acceptance of their pain such that vital life functions and engagements were not disrupted. Indeed, the community survey indicated that “working with pain” was much more common than lost work days due to pain. Blyth et al. thus commented that complete relief of pain was not a prerequisite for continual productivity or gainful work engagement [5]. McCracken noted the essence of acceptance in the context of chronic pain as “a process of flexible and practically effective action, free from unnecessary and unhealthy restriction by the experience of pain” [34]. Successful application of acceptance requires a patient to firmly acknowledge that avoiding or controlling pain are “patently ineffective” strategies (McCracken et al.) [32]. The process of acceptance is, however, not a matter of resignation, positive thinking or accurate belief; rather, acceptance has close similarity to the process of mindfulness — which advocates “full, present-focused, open and non-defensive attention to experience”, including pain, so much so that awareness of pain is allowed but without succumbing oneself to its disruptive interference (Kabat-Zinn) [26].

Positive versus negative affect Chronic pain patients may need to learn to accept that pain is unlikely to resolve in the short term before they are able to rebuild satisfaction and pleasures in their life. Positive affect concerns pleasure, satisfaction, sense of personal growth and self-liking. Chronic pain patients differ significantly from control subjects in their responses to the Depression, Anxiety and Positive Outlook Scale with elevated responses to depressive items like “I feel like a failure”, anxiety items like “I get a frightened feeling, as if something awful is about to happen”, and much subdued responses to positive outlook items like “I feel cheerful”, “I look forward with enjoyment to things”, “I can laugh and see the funny side of things” (Pincus et al.) [40]. While depression, anxiety and high neuroticism diminished the effectiveness of many chronic pain treatments (Wasan et al.) [59], higher levels of

average and weekly positive affect predicted lower pain and stress (Zautra et al.) [60]

Personality and other psychiatric morbidities Axis II diagnoses, i.e. personality disorders, are common in the chronic pain populations. Fishbain reported over-representation of passive-aggressive personality disorders and conversion disorders (somatosensory types) in male compensation patients with chronic pain while the noncompensation chronic pain patients were overly represented in compulsive personality [18]. In addition, over half of the chronic pain patients studied had a personality disorder diagnosis with 15% having passive/aggressive personality disorder and 25% having a compulsive personality type. Substance abuse was also more prevalent in chronic pain populations [18]. Sansone et al. found a high prevalence of borderline personality disorder and childhood abuse in patients with pain syndromes [47]. It was hypothesised that chronic pain problems may be a common manifestation with borderline personality features having self-regulatory difficulties. They also cautioned that “chronic pain syndromes meld well with the dynamics of borderline personality disorder including, for example, the need for frequent appointments (i.e. the attachment dynamics), extensive use of medications (i.e. oral self-regulation difficulties) and dependency issues”. Malmgren-Olsson et al. reported similar findings, noting that chronic pain patients had a personality profile characterised with high harm avoidance; low self-directedness; cautiousness, insecurity, pessimistic traits; difficulties accepting responsibility; lack of long-term goals; and chronic low self-esteem and struggles with identity [31]. Elevated Minnesota Multiphasic Personality Inventory (MMPI) scores on hypochondriasis and hysteria were noted to predict subsequent increases in chronic pain incidence [1, 49]. A more recent proposal by Gatchel et al. noted a “disability profile” in MMPI scores [20]. The MMPI-2 was administered to 1,489 chronic disabled spinal disordered patients with an average of 17 months of disability. Of all the chronic patients studied, less than 7% had a normal profile. In contrast, over half of the patients were classified into the disability

592 Peter W.H. LEE, Amy S.M. FUNG

profile defined as having four or more clinical scales elevated above a T-score of 65. It was argued that such individuals do not have any one particular coping method in their lives and, therefore, often experience severe emotional distress when under stress. The disability profile predicted negative response to treatment as well as delayed recovery. Repeated reports of personality problems implicated in chronic pain syndromes seem logical and understandable. Idiosyncratic and personal weaknesses must be considered given the fact that the same level of injuries, nociceptive stimulation and painful sensations gives rise to multiple and complex outcomes. Clinicians need to be alert to the presence of a host of personality disorders in their chronic pain patients, as without heeding or controlling such negative personality factors, treatments offered may end up being overly simplistic and unrealistic.

Anger and neuroticism Expressive styles characterised by direct verbal and/ or physical expression have been noted to impact on pain responses. Pilowsky and Spence noted that patients with intractable pain had a higher incidence of anger inhibition compared to a control group with other illnesses [37]. Bruehl et al. on the other hand, reviewed the current findings and found increased chronic pain problems with “trait angerout”, i.e. a habitual tendency and preference to manage angry emotions through direct expression [8]. Trait anger-out was also associated with functional disability (Duckro et al.) [13] and poor response to conventional treatment (Burns et al.) [9]. Bruehl et al. found a high association between depression, anger-out, general neuroticism (greater willingness and tendency to endorse symptoms of any kind), negative affect and pain responses [8]. The core dimension of neuroticism was regarded by Eysenck and Eysenck as being emotional instability and hypersensitivity [17]. Neurotic individuals tended to be emotionally unstable, sensitive to bodily states and present with a wide range of health complaints. Wade et al. noted that neuroticism was associated with negative pain beliefs, predicted poor abilities to endure pain and low confidence that pain will be cured [58]. Asghari et al. summarised the literature and noted that neuroticism may be associated with cognitive processes which prompted other negative prognostic factors in pain

outcome, including unhelpful pain-related beliefs, low flexibility, high self-blame and propensity towards catastrophic thinking [3]. Individuals with neurotic personalities are thus at higher risk for emotional impact and illness behaviour when faced with chronic pain.

Litigation Patients involved in compensation and litigation issues are caught in a bind where recovery may actually work against them and reduce the compensation award. Litigation also predisposes and fixates the patient’s attention on complaints and disabilities rather than wellness. Rohling et al. conducted a meta-analysis of 32 studies that compared patients in compensation situations with those who were not, and noted that the former consistently reported more pain and poorer treatment efficacy [45]. Rohling et al. therefore advised caution when patients who have compensation issues are considered for surgery. Robinson et al. also reported poorer treatment responses in compensation patients [43]. They evaluated 2,032 patients claiming workers’ compensation who had undergone pain centre treatment versus no treatment and noted a rather disappointing result that there was “no evidence that pain center treatment alters 2-year time loss status of already disabled workers”. Teasell reviewed the relevant literature and noted that indeed increased injury claim rates were associated with increased compensation rates, and that financial compensation was positively correlated with time off work [52]. He concluded that there is “moderate evidence that compensation influences chronic pain disability” and that “workers’ compensation status, particularly when combined with higher pain intensities, is associated with a poorer prognosis for treatment of patients with chronic musculoskeletal pain”. In a similar note, Blyth et al. in a telephone survey conducted on 484 chronic pain patients in the community noted that litigation for chronic pain was “strongly” associated with higher levels of pain-related disability, over and beyond other factors associated with poorer functional outcomes [5]. However, Mendelson in a review noted that not all patients recovered after settlement of litigation, and that for those who returned to work, the trend was towards less physically demanding and lower paying jobs [36].

Psychological Management in Chronic Pain 593

The weight of the evidence, however, points to the finding that litigation is a generally poor prognostic factor. Tait et al. cautioned that litigation may be seen as being a coping response for patients who are distressed by the adversarial nature of the workers’ compensation system, and that employment of a lawyer served to delay recovery and settlement [50]. Rainville et al. provided convincing data to indicate that compensated patients reported less improvement in pain, depression and disability even controlling for baseline and injury variables, and cautioned that patients are likely to be reluctant to report improvement when they are strongly reinforced by the benefits of compensation [42]. Baldwin even pointed to a potential “moral hazard” when insurance provides incentives for workers to engage in behaviours that increase the risk of covered losses, including an incentive to file workers’ compensation claims, extend injuryrelated durations of work absence and less incentive to avoid injuries [4]. Litigation and compensation issues may be important in affecting the outcomes of pain patients, both on their own and by intensifying other vulnerability factors associated with chronicity, as well as perpetuating a sedentary and non-productive lifestyle through secondary gains. One of the clinical issues related to compensation and litigation, though, is how to best recognise and differentiate individuals in litigation who require active treatment from those who would not for the time being, at least, benefit from active treatment. Some such patients may be simply malingering for the obvious financial benefit, as Case C illustrated. Other patients may, however, be hampered by psychological and social factors beyond the original injury. Lozito noted marked differences on the one hand of those who faked their disabilities and “those who truly do suffer from serious physical conditions, and must depend on workers’ compensation for their income” [29].

Workplace related factors The issue of work-related injuries points to yet another salient consideration of fitting rehabilitation measures/treatments to individuals. Baldwin reviewing the available literature noted that with work-related back injuries, light work accommodation rather than any other prevalent treatment approaches made a difference in success

in returning to work [4]. In addition, variables unrelated to traditional treatment focus, e.g. worker attitudes, such as fear of job loss in weak labour markets, prompted more positive attitudes towards return to work. Physically demanding work predicted higher disability, while job accommodations/modifications in the workplace were associated with shorter duration of disability. Worse psychosocial outcomes were noted in workers who blamed work factors for their injury and pain (as opposed to blaming themselves or other factors), who rated their relations with coworkers as poor, or who had low expectations of recovery (Crook et al.) [12]. Prognostic factors outside of the health care system have been highlighted as being important in reducing occupation-related disabilities after injury, including expectations of recovery, perception of health change, occupational stability, skill discretion at work, co-worker support, workplace offers of arrangement (in terms of flexible working hours or modified duties), and response of the employer and the workers’ compensation system (Hogg-Johnson et al.; Schultz) [24, 48].

Guidelines for Psychological Interventions Brown at al. cautioned that “myths, misconceptions, and false dichotomies, which stem from mindbody dualism, continue to pervade general medical and psychological thinking about pain” [7]. In terms of treatment and rehabilitation, while operant behavioural approaches (Fordyce) [19], cognitive behavioural approaches (Turk et al.) [53], relaxation and biofeedback (Eccleston et al.; Janicke et al.) [15, 25] have shown promise and support for their efficacy, the key to effective treatment lies in considering the person as a whole (rather than simply an organ in pain). Effective application of behavioural therapy, relaxation or cognitive treatments, physical therapies, analgesic medications, or combinations of treatments rests on deciding accurately when, how and why certain treatment/s may be appropriate and effective for this patient with his/her unique configuration of chronic pain problems. To this purpose, understanding of the process and mechanism underlying/maintaining chronic pain in “this” particular patient is required. As McCracken et al. rightly asserted, “the next generation of research into cognitive and behavioral therapies for chronic pain will no longer focus on

594 Peter W.H. LEE, Amy S.M. FUNG

establishing the general effects of treatment, but on specific processes of treatment, derived either pragmatically or theoretically” [33].

temporary relief may eventually lead to an undue overemphasis and confinement of life functions by painful sensations, thoughts and pain-related fears.

Incorporating relevant findings and clinical observations, a system of therapeutic techniques collectively named acceptance and commitment therapy (ACT) shows particular promise with good clinical sense and an increasing track record of empirical evidence (Hayes et al.) [22, 23]. Acceptance and commitment therapy has evolved over the past 10 years or so, is flexible, theory driven and places due emphasis on the reality situation of chronic pain patients.

Emotional avoidance Multiple tactics are employed to control emotional responses to pain, including suppression, distraction and emotional numbing. Many pain patients focus instead on their sense of being wronged, on their negative experiences with medical personnel, or on the dire need to have the pain go away.

Instead of focusing on or getting rid of pain at all costs, the focus of ACT is on maximising functions and maintaining emotional balance in patients with intractable pain conditions (Hayes et al.) [22, 23]. A basic premise of the approach lies in the observation that “the life-crushing effects of pain” in chronic pain syndromes “requires more than pain per se”. Robinson et al. noted a strong “unwillingness” dimension in chronic pain patients [44]. The unwillingness to accept a degree of pain and functional limitations often compels patients into thinking patterns, behavioural limitations and emotional responses which serve paradoxically to increase disability and impairment. The focus of assessment and management in ACT is multifold and targets behavioural avoidance, emotional avoidance, fusion with pain related thoughts and life directions issues (Robinson et al.) [43].

Behavioural avoidance Behavioural avoidance is presented in different forms, and often manifests as distancing from work, leisure and social activities due to reduction of pain or anticipatory avoidance of pain. Interpersonal contacts are usually those which support a life role of being a chronic pain patient. Pain associated behaviours such as irritability, outbursts and selfdamaging remarks often drive the person further away from resolving the pain-generated problems. The use of pain medications and related devices, with an accompanying increase in use of comfort behaviours (warm-baths, stretching, use of massage and pain-relieving patches) with the primary purpose of reducing pain, which while offering

Fusion with thoughts about pain Over time, patients with chronic pain may have their entire life dictated by pain as they become increasing prone to have pain-related thoughts even when they are not in pain. Robinson et al. provided an interesting example where a chronic pain patient reported a current pain rating of 6 and noted that it was lower than the average of 7 for the previous week [43]. Five minutes later, she started to cry and rub a body part, complaining “I can’t take this pain anymore.” The unwillingness to experience pain, plus thoughts and feelings associated with pain, may paradoxically compel the patient to fixate on pain avoidance and thereby fuse their daily existence with pain-related motivations. In other cases, fusion may also be evident in the patient’s story about their pain and suffering, e.g. with right and wrong evaluations (“my employer forced me…”, “I hated my doctors who ignored my complaints”), or a rigid sense of normality (e.g. “no one should have to suffer any degree of pain”, “I never had such pain sensations before; it must signify something is still very wrong with my body”). Life direction Chronic pain patients are often out of touch with their previous life goals and values. Helpful discussions may be conducted during therapy where inconsistencies between what the patient values and what is currently being done in life can be highlighted. The patient’s motivation can then be reoriented to considering the best ways to fulfil his/her life goals and values rather than reduction of pain per se. The ACT treatment involves “questioning the very basic assumptions — that the patient may have staked his quality of life on”. Multi-treatment foci can be developed for each patient to fit his/her situation. Robinson et al.

Psychological Management in Chronic Pain 595

provide numerous examples of potentially useful interventions as below [43]:

Auditing the drug regime The patient may be helped to audit the effectiveness of their drug regime and the impact on their overall quality of life. In many cases, patients may “discover” that pain medications reduce pain to some extent — in the short run, but run counter to their overall quality of life. Creative hopelessness Therapeutic work may start from the clinician trying to understand what the patient wants from treatment and then list all the efforts and solutions that the patient has tried to resolve the chronic pain. In engaging the patient in analysing “what have you tried, how has it worked, what is it costing you?”, etc., both the clinician and the patient may arrive at the conclusion that anything he/she has tried had not really made a difference in his/her life. A different treatment proposal may thus be made, i.e. to manage the problem of pain to make it less distressing or less of a barrier to doing the things the patient wants to do, rather than to try to unrealistically get rid of it altogether. In Robinson et al.’s terms, it means embarking on the “first act of willingness”, i.e. a choice to stop doing something that does not work [43]. The agenda consists of focusing on the desired outcomes in life (rather than pain) and how even without really solving the pain problem, the patient could become more effective in fulfilling his/her life goals, e.g. developing a better relationship with family members, having more peace of mind, enjoying daily life activities more, seeing more friends and making himself useful despite the pain. Reducing control Chronic pain patients often try hard to control their pain, which turns out to be ineffective. However, the fixation on gauging and controlling pain remains. Increasingly, the patient becomes locked into a preoccupation with pain. In ACT, a message that is often related to patients is that pain per se may not be lethal; rather, what we do about pain makes it toxic. With increasing awareness, patients may be better helped to reduce intentional avoidant behaviours and feelings, to accept a degree of pain and negative feelings, yet without allowing pain to be the insurmountable obstacle in life.

Valuing Choice, decision and responsibility are important values to promote. Robinson et al. pointed out that “the very essence of chronic pain patients is the justification of actions (or lack thereof ) by pointing to pain” [43]. Buried in this lexicon is the crippling and unworkable assumption that “A person can’t just go out and make something of their life when pain is present. Pain is the antithesis of what a healthy life is supposed to look like.” Therapeutic work needs to highlight and convince patients that shift is possible. Working on a better sense of choice and decision with patients often leads on to more value driven (rather than pain motivated) changes. •

•

Building patterns of committed actions. Using principles of behaviour therapy, therapeutic work focuses on changing contingencies that may be reinforcing maladaptive pain focus and behaviours. Acceptance and commitment therapy, however, goes a step further and emphasises preparing the patient well before committing to actions, by forming a better understanding of the futility of the coping, noting the devastating effect of catastrophic thoughts in relation to pain and the futility of aiming for total pain elimination. Instead, chronic pain patients are supported to increase their willingness to have pain, accept it for what it is and embark on committing to actions necessary for building a more meaningful life despite pain. More adaptive behaviours for a better valued life can then be built which are long lasting and more internally motivated Use of group processes. Groups offer validation and freedom from self-isolation. While some chronic pain patients may wrongly believe that their condition is unique and no one else could understand them, “coming into a room full of chronic pain patients with the same belief can be a real wake up call” (Robinson et al.) [43].

Accepting the premise that effective means should be provided to reduce and eradicate pain, the therapeutic aims of ACT, however, do not principally focus on reducing pain per se, but target reduction of the distressing and disabling influences of pain as they concern important areas in the patients’ everyday lives (McCracken et al.) [33]. Robinson et al. noted that ACT is a set of methods which may help the patient obtain a high quality

596 Peter W.H. LEE, Amy S.M. FUNG

of life, whether pain continues or not and whether the patient is compensated for suffering or not” [43]. In a treatment trial where 108 chronic pain patients went through a 3- to 4-week residential or hospital-based ACT programme, McCracken et al. noted significant improvements in the patients’ emotional, social and physical functioning [33]. Improvements were maintained at 3 months’ follow-up. The treatments were described as being comprehensive and interdisciplinary based, with multiple foci designed to increase the patients’ willingness to face uncomfortable thoughts and feelings, and to focus their efforts on behaviours which improve functioning in the long run rather than serving some momentary urge or feeling. Physical exercises were designed for graded exposure to feared sensations and increased activation. Health habits and choosing meaningful directions in life (rather than that of a chronic pain sufferer) were nurtured. Patients learned and became aware of the failure of strategies which aimed only at pain control and reduction. They were also exposed to their habitual thoughts and feelings related to the pain experience, and went through subsequent habit reversal training and mindfulness meditation exercises to help distance themselves away from negative and/or catastrophic thinking regarding pain. Relaxation exercises to improve body awareness and productive functioning, coupled with sensation focus exercises to highlight the possibility of activity and enjoyment despite pain being present, and exercises to raise the social effects of overt pain displays were also scheduled into the treatments (please refer to Chapter 38 for more details). At the end of treatment and at 3-month followup, significant changes were noted in reduced depression, reduced physical disability, reduced psychosocial disability, reduced rest hours related to pain, improved directly measured activity performance, reduced analgesic use and visits to doctors, and improved work status. The improvements were noted to be related to activity engagement (regardless of pain) and willingness to accept the pain with little need to accept or control the painful experience.

Summary and Conclusion While chronic pain may be maintained by catastrophic thinking in one patient, secondary gains and personality problems may account for the distress and sufferings of another patient. Routinely going beyond standard psychological and psychiatric diagnosis is advocated. Effective management of chronic pain requires a realistic formulation and understanding of the unique processes and mechanisms triggering, maintaining and aggravating pain in each individual patient. There is no one effective formula for assessment and treatment of chronic pain. While the format of assessment may be similar, the contents involved in assessing each individual patient may markedly differ. Clinicians have to keep abreast of the latest and ever-changing research findings in the field to guide their assessment and case formulations. All chronic pain goes through an acute stage. There is hope that with early assessment and intervention for high-risk individuals, pain that is managed well at the early stage may not progress into chronicity, thereby short-circuiting unnecessary secondary distress and handicap. Chronic pain, however, is like a tumour. Pain and accompanying psychosocial factors which are poorly managed grow and kindle additional handicaps and entangled difficulties. The diverse pathological factors, if not detected and dealt with at an early stage, may spread — not only afflicting the vulnerable individual with pain, but eventually wreck his whole life and diminish the very essence of life’s purpose, enjoyment and meaning. Sensitivity, good will and effective clinical interpersonal skills on the part of the clinician often work well in fostering the patient’s trust and collaboration. Specific interventions aimed at preservation of the patient’s morale, life quality, goals in life and aspirations towards the future are important. Patients need to be helped to understand the nature and harm (or lack of harm) of any residual pain which cannot be relieved by existing medical means, to learn to accept them into their life schemes, minimising undue sufferings, impairment and curtailment of useful functions, and without being robbed of life’s intrinsic satisfactions and joy.

Psychological Management in Chronic Pain 597

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30.

Applegate KL, Keefe FJ, Siegler IC, et al. Does personality at college entry predict number of reported pain conditions at mid-life? A longitudinal study. J Pain 2005;6:92–7. Andersson GBJ. Epidemiological features of chronic low-back pain. Lancet 1999;354:581–5. Asghari A, Nicholas MK. Personality and pain-related beliefs/coping strategies: A prospective study. Clin J Pain 2006;22:10–8. Baldwin ML. Reducing the costs of work-related musculoskeletal disorders: Targeting strategies to chronic disability cases. J Electromyogr Kinesiol 2004;14:33–41. Blyth FM, March LM, Nicholas MK, et al. Chronic pain, work performance and litigation. Pain 2003;103:41–7. Boersma K, Linton SJ. Psychological processes underlying the development of a chronic pain problem. Clin J Pain 2006;22:160–6. Brown KS, Folen RA. Psychologists as leaders of multidisciplinary chronic pain management teams: A model for health care delivery. Prof Psychol Res Pr 2005:36:587–94. Bruehl S, Chung OY, Burns JW. Anger expression and pain: An overview of findings and possible mechanisms. J Behav Med 2006;29:593–609. Burns JW, Johnson BJ, Devine J, et al. Anger management style and prediction of treatment outcome among male and female chronic pain patients. Behav Res Ther 1998;36:1051–62. Cochiarella L, Andersson GBJ, eds. Guides to the Evaluation of Permanent Impairment, 5th edn. Chicago: American Medical Association Press, 2001. The Committee on Handicaps In Caring for people with physical impairment: The journey back, Group for the Advancement of Psychiatry, American Psychiatric Press. Washington DC, London, England, 1993. Crook J, Milner R, Schultz IZ, et al. Determinants of occupational disability following a low back injury: A critical review of the literature. J Occup Rehabil 2002;12:277–95. Duckro PN, Chibnall JT, Tomazic TJ. Anger, depression and disability: A path analysis of relationships in a sample of chronic posttraumatic headache patients. Headache 1995;35:7–9. Eccleston C, Crombez G. Pain demands attention: A cognitive-affective model of the interruptive function of pain. Psychol Bull 1999;125:356–66. Eccleston C, Yorke L, Morley S, et al. Psychological therapies for the management of chronic and recurrent pain in children and adolescents. Cochrane Database Syst Rev 2003;(1):CD003968. Ehlers A, Maercker A, Boos A. Posttraumatic stress disorder following political imprisonment: The role of mental defeat, alienation, and perceived permanent change. J Abnorm Psychol 2000;109:45–55. Eysenck HJ, Eysenck SB. The orthogonality of psychoticism and neuroticism: A factorial study. Percept Mot Skills 1971;33:461–2. Fishbain DA, Goldberg M, Labbe E, et al. Compensation and non-compensation chronic pain patients compared for DSM-III operational diagnoses. Pain 1988;32:197–206. Fordyce WE. Behavioral Methods for Chronic Pain and Illness. St. Louis: CV Mosby, 1976. Gatchel RJ, Mayer TG, Eddington A. MMPI Disability Profile: The least known, most useful screen for psychopathology in chronic occupational spinal disorders. Spine 2006;31:2973–8. Goubert L, Crombez G, Hermans D. Low back pain, disability and back pain myths in a community sample: Prevalence and interrelationships. Eur J Pain 2004;8:283–9. Hayes SC, Strosahl K, Wilson KG. Acceptance and Commitment Therapy: An Experiential Approach to Behavior Change. New York: Guilford Press, 1999. Hayes SC, Strosahl KD, Wilson KG, et al. Measuring experiential avoidance: A preliminary test of a working model. Psychol Rec 2004;54:553–78. Hogg-Johnson S, Cole DC. Early prognostic factors for duration on temporary total benefits in the first year among workers with compensated occupational soft tissue injuries. Occup Environ Med 2003;60:244–53. Janicke DM, Finnev JW. Empirically supported treatments in pediatric psychology: Recurrent abdominal pain. J Pediatr Psychol 1999;24:115–27. Kabat-Zinn J, Lipworth L, Burney R. The clinical use of mindfulness medication for self-regulation of chronic pain. J Behav Med 1985;8:163–90. Lancourt J, Kettelhut M. Predicting return to work for lower back pain patients receiving workers’ compensation. Spine 1992;17:629–40. Lethem J, Slade PD, Troup JDG. Outline of a fear avoidance model of exaggerated pain perceptions. Behav Res Ther 1983;21:401–8. Loeser JD. Pain: Disease or dis-ease? The John Bonica Lecture: Presented at the Third World Congress of World Institute of Pain, Barcelona 2004. Pain Practice 2005:5:77–84. Lozito M. Chronic pain: The new workers’ compensation? Case Manager 2004;61–3.

598 Peter W.H. LEE, Amy S.M. FUNG

31. Malmgren-Olsson EB, Bergdahl J. Temperament and character personality dimensions in patients with nonspecific musculoskeletal disorders. Clin J Pain 2006;22:625–31. 32. McCracken LM, Vowles KE, Eccleston C. Acceptance of chronic pain: Component analysis and a revised assessment method. Pain 2004;107:159–66. 33. McCracken LM, Vowles KE, Eccleston C. Acceptance-based treatment for patients with complex, long standing chronic pain: Preliminary analysis of treatment outcome in comparison to a waiting phase. Behav Res Ther 2005;43:1335–46. 34. McCracken LM. A contextual analysis of attention to chronic pain: What the patient does with their pain might be more important than their awareness or vigilance alone. J Pain 2007;8:230–6. 35. Melzack R. Evolution of the Neuromatrix Theory of pain. The Prithvi Raj Lecture: Presented at the Third World Congress of World Institute of Pain, Barcelona 2004. Pain Practice 2005;5:95–4. 36. Mendelson G. Compensation and chronic pain. Pain 1992;48:121–3. 37. Nicholas M, Asghari A. Investigating acceptance in adjustment to chronic pain: Is acceptance broader than we thought? Pain 2006;124:269–79. 38. Niv D, Devor M. Chronic pain as a disease in its own right. Pain Practice 2004;4:3:79–181. 39. Pilowsky I, Spence ND. Pain, anger and illness behavior. Psychosom Med 1976;20:411–6. 40. Pincus T, Williams AC de C, Vogel S, et al. The development and testing of the depression, anxiety, and positive outlook scale (DAPOS). Pain 2004;109:181–8. 41. Polatin KB, Kinney RK, Gatchel RJ, et al. Psychiatric illness and chronic low-back pain. Spine 1993;18:66–71. 42. Rainville J, Sobel JB, Hartigan C, et al. The effect of compensation involvement on the reporting of pain and disability by patients referred for rehabilitation of chronic low back pain. Spine 1997;22: 2016–24. 43. Robinson JP, Fulton-Kehoe D, Martin DC, et al. Outcomes in pain center treatment in Washington State Workers’ Compensation. Am J Ind Med 2001;39:227–36. 44. Robinson P, Wicksell RK, Olsson GL. ACT with chronic pain patients. In Hayes SC and Strosahl KD, eds. A Practical Guide to Acceptance and Commitment Therapy. New York: Springer, 2004:315–45. 45. Rohling ML, Binder LM, Langhinrichsen-Rohling J. Money matters: A meta-analytic review of the association between financial compensation and the experience and treatment of chronic pain. Health Psychol 1995;14:537–47. 46. Romano JM, Turner JA. Chronic pain and depression: Does the evidence support a relationship? Psychol Bull 1985;97:18–34. 47. Sansone RA, Whitcar P, Meier BP, et al. The prevalence of borderline personality among primary care patients with chronic pain. Gen Hosp Psychiatry 2001;23:193–7. 48. Schultz IZ, Crook J, Meloche GR, et al. Psychosocial factors predictive of occupational low back disability: Towards development of a return-to-work model. Pain 2004;107:77–85. 49. Sternbach RA. Pain Patients: Traits and Treatments. New York: Academic Press, 1974. 50. Tait RC, Chibnall JT, Richardson WD. Litigation and employment status: Effects on patients with chronic pain. Pain 1990;43:37–46. 51. Tang NKY, Salkovskis PM, Hanna M. Mental defeat in chronic pain: Initial exploration of the concept. Clin J Pain 2006;23:222–32. 52. Teasell RW. Compensation and chronic pain. Clin J Pain 2001;17:S46–S51. 53. Turk DC, Meichenbaum D, Genest M. Pain and Behavioral Medicine: A Cognitive-Behavioral Perspective. New York: Guilford Press, 1983. 54. Turk DC, Okifuji A. Perception of traumatic onset, compensation status, and physical findings: Impact on pain severity, emotional distress and disability in chronic pain patients. J Behav Med 1996;19:435–53. 55. Turk DC, Monarch ES. Biopsychosocial perspective on chronic pain. In Turk DC, Gatchel RJ, eds. Psychological Approaches to Pain Management, 2nd edn. New York, London: Guilford Press, 2002:3–29. 56. Vlaeyen JWS, Kole-Snijders AMJ, Boeren RGB, et al. Fear of movement/(re)injury in chronic low back pain and its relation to behavioral performance. Pain 1995;62:363–72. 57. Waddell G, Newton M, Henderson I. A Fear-Avoidance Beliefs Questionnaire (FABQ) and the role of fear-avoidance beliefs in chronic low back pain and disability. Pain 1993;52:157–68. 58. Wade JB, Doughetry LM, Hart RP. A canonical correlation analysis of the influence of neuroticism and extraversion on chronic pain, suffering and pain behavior. Pain 1992;51:67–73. 59. Wasan AD, Daar G, Jamison R. The association between negative affect and opioid analgesia in patients with discogenic low back pain. Pain 2005;117:450–61. 60. Zautra AJ, Johnson LM, Davis MC. Positive affect as a source of resilience for women in chronic pain. J Consult Clin Psychol 2005;73:212–20.

38

Tak Yi CHUI, Michael K. NICHOLAS

Functional Rehabilitation and Cognitive Behavioural Interventions

INTRODUCTION UNDERSTANDING FUNCTIONING AND DISABILITY APPLICATION OF ICF CONCEPTS IN FUNCTIONAL REHABILITATION OF PATIENTS WITH CHRONIC PAIN DEFINING DISUSE AND DECONDITIONING IN REHABILITATION OF PATIENTS WITH CHRONIC PAIN MEASURING AND ASSESSING ACTIVITY SPECIFIC ISSUES IN FUNCTIONAL REHABILITATION IN PATIENTS WITH CHRONIC MUSCULOSKELETAL PAIN Patient evaluation Exercise and reactivation Graded exposure Functional capacity evaluation EFFECTS OF COMPENSATION AND LITIGATION ON REHABILITATION USING COGNITIVE BEHAVIOURAL THERAPY

Introduction Pain is a common phenomenon in many medical conditions, and its management is an essential part of the comprehensive and holistic care of the individual patient. Good pain management is advocated by many organisations, including The Joint Commission for hospital accreditation (in the US), which recommended pain be considered as the fifth vital sign [61]. Acute pain (e.g. associated with a fracture, inflammatory arthritis, myocardial infarction, herpes zoster) will usually subside when the original pathology is removed or controlled by treatment. Such pain is relatively short lasting and usually will not be a major or persistent barrier to rehabilitation. However, in some patients, pain persists and becomes refractory to treatment. It may be disproportionate to, or not accountable by, clinical findings and results from investigations. This type of pain often leads to significant emotional distress as well as secondary physical, psychological and behavioural changes which compound disability and handicap. If poorly managed, persisting pain has a high likelihood of severely limiting rehabilitation outcomes. There are many clinical conditions that can give rise to chronic or persistent pain, and while their specific natures may require different types of intervention or emphasis, typically they have enough in common to share general rehabilitation principles. It is beyond the scope of this chapter to explore all possible chronic pain conditions. Whenever appropriate, some of the more common chronic conditions will be used for illustration.

600 Tak Yi CHUI, Michael K. NICHOLAS

Understanding Functioning and Disability In 2001, the World Health Organization (WHO) published a revised version of the International Classification of Impairment, Disability and Handicap (ICIDH-2). This was later renamed the International Classification of Functioning, Disability and Health (ICF). The ICF aimed to offer a more precise operational definition of health and was endorsed by the World Health Assembly of the WHO for the purposes of reporting health situations in member states [21]. In the ICF, the central theme is how people live with their conditions. The assessment focuses on the person’s functioning, rather than a description of their disease or injury. Functioning and disability are viewed as outcomes of interactions between health conditions (diseases, disorders and injuries), and contextual factors [14, 21, 42]. Details about the ICF can be found in the ICF website (www3.who.int/icf ) [54]. The ICF framework is summarised as follows: “Functioning” (a positive description) is an umbrella term encompassing all body functions (physical and psychological), activities (execution of a task or action) and participation (involvement in a life situation). Similarly, “disability” (a negative description, the “reverse” of functioning) serves also as an umbrella term for impairment (versus functions), activity limitations or participation restrictions.

METHODS IN FUNCTIONAL REHABILITATION IN PEOPLE WITH CHRONIC PAIN Principles of cognitive behavioural therapy Treatment planning/preparation Goal setting Collaboration Re-formulation Format Skills Multidisciplinary team Content Planning for maintenance after pain management REFERENCES

The domains of activity and participation include, but are not restricted to, learning and applying language, general tasks and demands, communication, mobility, self-care, domestic life, interpersonal interactions and relationships, major life areas (such as education, remunerative employment), community, and social and civic life. The evaluation of activity and participation includes two qualifiers: capacity and performance. The capacity qualifier describes an individual’s ability to execute a task or an action. This construct describes the highest probable level of functioning of a person in a given domain at a given moment. The performance qualifier describes what an individual does in his/her current environment. Since the current environment always includes the overall societal context, performance can also be understood as “involvement in a life situation” or the “lived experience” of people in their actual context. The “current environment” can include assistive devices or personal assistance that an individual may use to perform actions or tasks. Contextual factors include external environmental factors and internal personal factors (Table 38.01). Environmental factors

Functional Rehabilitation and Cognitive Behavioural Interventions 601

Table 38.01

Contextual factors

Environmental factors • Products and technology (e.g. food, medicines, design, construction and building products and technology of buildings) • Natural environment and man-made changes to environment (e.g. climate, sound) • Support and relationships (e.g. immediate family, friends, people in positions of authority, health professionals) • Attitudes (e.g. individual attitudes of immediate family members/health professionals, societal attitudes and social norms, practices and ideologies) • Services, systems, and policies (e.g. those related to housing, transportation, legal, social security, health, labour and employment) Personal factors • Demographics (e.g. gender, age, race/ethnicity, social background, education, profession) • Habits, sexual orientation • Past and current experience/life events • Overall behaviour pattern, coping styles, character • Other factors that may impact on functioning, or affect the experience of disability on a personal level.

may be further subclassified with “qualifiers”, according to whether they are facilitators or barriers/hindrances.

Application of ICF Concepts in Functional Rehabilitation of Patients with Chronic Pain Appropriate and detailed assessment of the presenting problem, contributing factors and identification of treatment goals (or needs) in relation to the particular patient is an essential prerequisite for treatment planning. The ICF provides a comprehensive biopsychosocial framework for understanding the morbidities and issues to be addressed in an individual with chronic pain and the context for intervention; the aim is to achieve optimal functioning. The original classification, with more than 1,400 categories, was found impractical and a simplified version has been

developed for the 12 most burdensome chronic conditions. This includes the musculoskeletal health conditions of low back pain, osteoarthritis, osteoporosis and rheumatoid arthritis. For these conditions, the comprehensive core sets and brief core sets were developed for comprehensive multidisciplinary assessment and clinical study respectively [16]. Although these tools are still considered preliminary and in need of further testing, they are intended for use in the following areas: clinical documentation and reports; description of patient’s functioning and the identification of intervention target categories and respective outcome categories; enabling patients and their families to understand and communicate with health professionals about their functioning and treatment goals; multiand interdisciplinary assessment in rehabilitation settings; legal expert evaluations; and use in disease or functioning-management programmes [120]. These tools provide an important step towards improved communication among health care providers and between these professionals and the patients, and other stakeholders. To illustrate how the ICF can help in the identification of the rehabilitation needs of patients with pain conditions, the ICF core set for low back pain is described in Table 38.02 [16]. As can be seen from the table, the core set provides a framework and classification for defining the typical spectrum of problems in functioning of patients with low back pain. The lists of problems in the comprehensive ICF core set serves to guide multidisciplinary assessments in patients with low back pain. Useful studies on the use of the ICF in the rehabilitation of various clinical conditions with chronic pain may be found in the literature [2, 15, 59, 110, 112, 138, 149, 150].

Defining Disuse and Deconditioning in Rehabilitation of Patients with Chronic Pain The terms disuse and deconditioning have been commonly employed in this field for some time, although their precise meanings are not always

602 Tak Yi CHUI, Michael K. NICHOLAS

Table 38.02 ICF categorization of components in the Comprehensive ICF Core Set for low back pain (reproduced with permission of Dr. A Cieza) [16] Body structure

Body functions

Activities and participation

Environmental factors

Spinal cord and related structures Structure of pelvic region Structure of lower extremity Structure of trunk Additional musculoskeletal structures related to movement

Temperament and personality functions Energy and drive functions Sleep functions Emotional function Experience of self and time functions Proprioceptive function Sensation of pain Exercise tolerance function Urination functions Sexual functions Mobility of joint functions Stability of joint functions Mobility of bone functions Muscle power functions Muscle tone functions Muscle endurance functions Motor reflex functions Gait pattern functions Sensations related to muscles and movement functions

Handling stress and other psychological demands Changing basic body position Maintaining a body position Transferring oneself Lifting and carrying objects Hand and arm use Walking Moving around Moving around in different locations Moving around using equipment Using transportation Driving Washing oneself Toileting Dressing Looking after one’s health Acquisition of goods and services Preparing meals Doing housework Caring for household objects Assisting others Basic interpersonal interactions Family relationships Intimate relationships Acquiring, keeping and terminating a job Remunerative employment Work and employment, other specified and unspecified Community life Recreation and leisure

Products or substances for personal consumption Products and technology for personal indoor and outdoor mobility and transportation Products and technology for employment Design, construction and building products and technology of buildings for public use Design, construction and building products and technology of buildings for private use Climate Vibration Immediate family Acquaintances, peers, colleagues, neighbours and community members People in positions of authority Health professionals Other professionals Individual attitudes of immediate family members Individual attitudes of acquaintances, peers, colleagues, neighbours and community members Individual attitudes of health professionals Individual attitudes of other professionals Societal attitudes Social norms, practices and ideologies Transportation services, systems and policies Legal services, systems and policies Social security services, systems and policies General social support services, systems and policies Health services, systems and policies Education and training services, systems and policies Labour and employment services, systems and policies

Functional Rehabilitation and Cognitive Behavioural Interventions 603

clear. Essentially, disuse has been used to describe states of physical immobility: “not using the musculoskeletal system”. Some authorities have also used the term disuse to describe inefficient use of the musculoskeletal system; an example in the pain population is the entity of “guarded movement” described by Main and Watson [72]. Bortz used the term disuse syndrome to describe the consequences of long-term inactivity in terms of five interdependent features: cardiovascular vulnerability, obesity, musculoskeletal fragility, depression and premature ageing [8]. Deconditioning has been used to describe changes in the body which result from long-term disuse [136]. A model for progression from acute pain to chronic pain, physical deconditioning syndrome, was developed to explain the end result of the interaction of physical and mental de-conditioning [77]. Physical deconditioning included muscle atrophy, decreased cardiovascular endurance, decreased neuromuscular co-ordination and a decreased ability to perform complicated repetitive tasks. Mental deconditioning referred to a range of behavioural and psychological problems that occur in response to chronic pain and the patients’ attempt to cope with that pain. It evolves from the initial stage of psychological distress (e.g. fear, anxiety and worry) to more pervasive problems (e.g. depression — learned helplessness; anxiety disorders — symptom magnification and anger). The interaction between the physical deconditioning and the stages of mental deconditioning was bidirectional. Reduced fitness from disuse could lead to despondency and that, in turn, could lead to further disuse and deconditioning through poor motivation. However, the apparently simple concepts of disuse, deconditioning and physical deconditioning syndrome should be treated with caution. Despite that a large proportion of those who develop chronic pain conditions experience significant diabilities [7], recent investigations have reported conflicting findings, at least in relation to chronic low back pain (CLBP). While many studies have reported that muscle strength was lower in CLBP patients relative to healthy controls, studies of aerobic fitness in these groups have been less consistent, with several studies reporting no difference between patients with CLBP and healthy controls [137]. Verbunt et al. concluded that “in patients with CLBP, physical deconditioning once more proves to be a general disuse-related problem instead of

a problem solely affecting the back muscle”, and suggested that higher pain intensity or psychological distress seemed to increase the inhibition of muscle activity, which leads to submaximal performance of specific tasks [136]. Others have also argued that the presence of disuse or physical deconditioning in patients with CLBP is actually doubtful [91]. Aerobic capacity was found to be similar in patients with CLBP and normal controls [154], while prerehabilitation aerobic capacity testing was a poor differentiator of post-rehabilitation outcome [104]. Two major behavioural models of disuse and disability have been described. They are the fearavoidance behaviour model and the suppressive behaviour model, which intended to explain why some patients with chronic low back pain, but not others, develop disuse-related deconditioning after the onset of back pain. The fear-avoidance model proposed that following the onset of pain, such as after an injury, if the individual holds fearful beliefs (especially catastrophic appraisals) about the pain and the possibility of further injury, s/he is likely to avoid activities that may aggravate the pain [141]. Over time this will lead to disuse, deconditioning and disability. At the same time, if the person persists with their escape and avoidance behaviours, the disability will be compounded as there will be no opportunities to correct the inaccurate expectations and beliefs about pain as a signal of threat. Eventually, this is likely to lead to mood disturbance, such as irritability, frustration and depression due to the loss of normal reinforcers. In contrast, the suppressive behaviour model [49] proposed that there is another subgroup of chronic pain patients who have a tendency to cope with pain using endurance strategies. This group appears to ignore their pain and by their suppressive behaviour, overload their muscles (overuse), which leads to muscular hyperactivity. In this group, deconditioning would not seem to be playing a causal role in their pain-related disability. They are likely to report a physical activity level that fluctuates dramatically over time in reaction to pain levels. They tend to persevere until increasing pain prevents further activity, then rest completely until the pain subsides or frustration over inactivity stimulates resumption of activity, resulting in the so-called “over-activity/under-activity” cycle.

604 Tak Yi CHUI, Michael K. NICHOLAS

This behaviour pattern may be related to a premorbid personality characterised by excessively high self-expectations (e.g. perfectionistic traits) and difficulties in accepting realistic limits, so there is a tendency to repeatedly overdo things leading to more pain and frustration. Interestingly, if this group then use analgesics to control their pain they are at risk of simply continuing their nonadaptive coping style but get into more trouble with overdoing, more pain and excessive drug use (see ref. 97 for a discussion of this). In both subgroups there is a need to find ways to modulate activity levels via strategies such as pacing to minimise under-doing and overdoing.

Measuring and Assessing Activity There is no consensus on ways of measuring and assessing activity. Accordingly, we need to weigh the available methods based on their psychometric properties (reliability and validity), their intended purposes and practical considerations, e.g. cost and time. Activity level assessment can be based on selfreport, diary or questionnaires. The validity of selfreports of activity is uncertain and patients tend to underestimate their activity level [58]. Objective measures might be more reliable, but there may be a problem with external validity (how well they relate to normal activities in the patient’s environment) and practicality concerns. Direct observation by an observer or video is generally reliable but too time consuming, and might only be used on a time sampled basis. A useful review of specific standardised functional tasks (e.g. walking a set distance or climbing stairs) has been described by different authors [115, 117]. Movement registration by accelerometry [108, 134] allows measurement of changes in the quantity of activities and change in the pattern of physical activities over time, providing the patient remembers to use the device. Other measures like physiological measures of energy consumption during activities, energy expenditure measurement, such as the doubly-labelled water technique, are too cumbersome, expensive and not practical in usual clinical settings.

Activity may be assessed in terms of specific activities (e.g. walking time or frequency of lifting a specified amount) or an estimate of how much certain classes of activity are limited due to pain (e.g. the Oswestry and Pain Disability Index). In these sorts of scales, a total score can be derived by summing the scores for different classes of activity (e.g. work, home, social). However, their accuracy has been questioned as there is a tendency for chronic pain patients to underestimate their own activity level. Nevertheless, such scores do provide an indication of activity performance as perceived by the patient and they can be used repeatedly to measures change as rehabilitation progresses [153]. In order to ensure that only activities relevant to the particular patient are assessed, some researchers have promoted the use of individualised patient specific measures [119]. This involves asking the patient which activities they would like to increase and as treatment progresses the patient rates the degree to which they have achieved these activity goals [23]. The advantage of this approach is that it only assesses activities relevant to the patient, as opposed to summary scores on a more generic scale. The disadvantage is that it doesn’t provide a standardised assessment (with known psychometric properties and normative data) which can assist the evaluation of groups of patients, especially in research contexts. Individualised goals can vary in size (e.g. “walk to the door without using a stick” versus “drive for 2 hours without stopping for a rest”) [63, 64].

Specific Issues in Functional Rehabilitation in Patients with Chronic Musculoskeletal Pain Patient evaluation A detailed evaluation establishes the foundation for therapeutic decision making. It should include a description and history of the chief complaints, including the impact of these on the patient and his/her lifestyle. These can be considered under headings such as functional history, psychological and social history, medications, allergy, diet, past medical/surgical history (Table 38.03) [80].

Functional Rehabilitation and Cognitive Behavioural Interventions 605

Physical examination should include an appropriate medical examination as well as a neuromuscular and functional examination [26]. Treatment response and compliance with treatment should be reviewed as well. The patient should be re-evaluated if new, or changes, in symptoms are reported. Optimal treatment may include a combination of pharmacological modalities, aids, interventional treatment, and psychological and social interventions, according to the outcome of the evaluation rather than a “one size fits all” approach. The use of informal carers may also need to be considered and supported when indicated. Outcomes should be evaluated and treatment regimens adjusted accordingly. The outcomes sought should reflect the patient’s wishes and their active participation in treatment planning and goal setting should be encouraged.

Table 38.03

Patient evaluation (where relevant)

Chief complaint

Description and history of presenting problems

Functional history

Impact of complaints on mobility, activities of daily living, household activities, community activities, cognition communication, vocation and the use of assistance devices

Psychological history

Psychiatric history, current mood disturbance, substance abuse, fear-avoidance behaviour, catastrophising, anxiety, self-efficacy

Social history

Social support, family relationships, living situation, vocational history, compensation and medicolegal status, sexual history, finances, inappropriate beliefs

Others

Medications, allergy, diet, medical/surgical history

Past treatment

Modalities of treatment, responses and compliance should be reviewed

Physical examination

Medical examination Neuromuscular and functional examination

Muscle weakness Different studies have demonstrated weakness related to painful conditions, e.g. patients with CLBP were shown to have a weaker torque during isokinetic contractions, in which the speed was controlled by accommodating the resistance [78]. Muscle strength evaluation is a basic component of function evaluation in many neurological and orthopaedic conditions which present with weakness and/or pain. However, the difficulties associated with measuring muscle power, which is a measurement of impairment, may be due to the inadequacies of evaluation tests (i.e. reliability, sensitivity and specificity). Manual muscle testing typically involves groups of muscles, depends on the examinee’s co-operation and is subject to his or her conscious and unconscious control [18]. Maximal effort is defined by the social context, including the standards and incentives it provides [122]. As mentioned earlier in relation to the 2005 study of Verbunt et al., there are other non-physical reasons for the reduction in muscle power in painful conditions [137]. For example, patients with chronic pain often avoid using the painful part as they fear that maximal contraction will lead to increase in pain or re-injury of the painful structure [142]. The contributions of regional muscle strength and pain to function loss and disability are complex and have been most widely studied in patients with CLBP. For example, in a trial on the lifting capacity of volunteers using functional capacity evaluation systems, Schenk et al. found that maximum force, endurance of the muscles involved in movement production and stabilisation of the trunk during movements in the sagittal plane, cardiovascular endurance, mobility and co-ordination ability, predicted only 18–35% of the lifting capacity [109]. Previously, Simmonds had advocated that although impairment tests can complement tests of function and may be useful in directing rehabilitation, it is often inappropriate to use impairment measures alone, and they should not be used as sole indicators of function [113]. For example, Mannion et al. found that in a randomised study of 136 CLBP patients undergoing three different exercise programmes, the most significant predictors of disability at baseline were, in decreasing order: pain, psychological distress, fearavoidance beliefs, muscle activation levels, lumbar

606 Tak Yi CHUI, Michael K. NICHOLAS

range of motions and gender [73]. At the end of a 3-month rehabilitation programme, although there were significant improvements in flexion, lateral bending and axial rotation, particularly in the group that was trained on devices, only changes in pain, psychological distress and fear-avoidance beliefs significantly accounted for the improvement in disability [73]. In measuring outcome of chronic pain rehabilitation, physical capacity measures (e.g. muscle strength measurement) are usually less important than measures of physical functioning, psychological functioning and patient satisfaction [116, 132]. Thus, while muscle power can be reduced in painful conditions, especially when they are chronic, this effect can be due to multiple causes. This means that simply prescribing strengthening exercises as a means of remedying the effect is unlikely to be sufficient in patients, and this is well supported by the research literature in patients with CLBP.

Gait Walking is often found to be impaired in patients with CLBP. In human bipedal locomotion, the spine, especially the lumbar spine, plays an active role. Walking is the product of spinal oscillations in all anatomical planes. Cyclic spinal loads are experienced many times in a day. Researchers have long observed that patients with CLBP walked more slowly, took shorter steps and did not show the symmetrical gait patterns evident in normal controls. Many of these patients also exhibited more pain behaviours (e.g. guarding, bracing, rubbing the painful area, grimacing and sighing) [55]. The pain adaptation model postulates that activity of the agonist muscle group is inhibited and that of the antagonist augmented to minimise movement of the painful segment [70]. Advanced gait analysis helps to understand pathokinesiology and shed insights on designing strategies for intervention. A three-dimensional kinematic analysis of lumbar spinal movements in patients with CLBP showed that the stride length is reduced (resulting in smaller steps), which might be interpreted as a rigid or more cautious walking pattern and serves as a protective way to reduce or avoid pain [144]. These patients demonstrated higher degrees of stride-to-stride variability, representing increased fluctuations in dynamic thoracic and pelvic oscillations. The explanation for this increased variability could

be impaired proprioception, resulting in less or inappropriate spatial, temporal, or kinetic information which is important for precise control over the timing of events in the gait cycle. With suboptimal synchronisation of different body segments, the quality of gait is influenced and thus the energy saving system of the spine during ambulation is reduced. In turn, the smaller steps pattern serves as a compensatory gait strategy to minimise the additional energy expenditure. A higher variability of tissue loading might also contribute to musculoskeletal dysfunction, namely the contraction of agonist and antagonist muscle groups [144]. In another study, Lamoth et al. found that at all walking speeds, the stride length was shorter in CLBP patients. They found a more rigid and less variable kinematic co-ordination in the transverse plane, and more variable co-ordination in the frontal plane, which seems to serve as a compensatory mechanism. Lumbar erector spinae activity was increased during the swing phase, which might reflect poorer co-ordination. Interestingly, in this study, actual pain intensity, anticipated pain, disability and fear-avoidance did not correlate with the kinematic and electromyographic variables. The need of a slower walking speed (which also helps to avoid antiphase thorax-pelvis coordination) was postulated to be an attempt to enhance the control and create a margin of safety to handle perturbations, especially the rotational perturbations between the lumbar and pelvic segments. Lamoth et al.’s findings suggested a need for developing new perspectives in measuring and training the trunk muscle co-ordination and gait pattern in CLBP patients. Importantly, training should not aim at increasing walking speed alone, but rather facilitation of a more desired trunk coordination pattern [60]. In a study of patients with fibromyalgia, Pierrynowski et al. found that although the walking speed, stride length and joint angular kinematics and ground reaction forces were similar to the control volunteer group, the internal muscle recruitment patterns were different. In forward propulsion at slow speed walking, normal controls would use ankle plantar flexors (ankle push), while fibromyalgia patients would use a lifting motion of the hip (hip pull) which normal people would only use in fast walking. The hip pull requires high energy expenditure and causes accelerated fatigue. This recruitment pattern

Functional Rehabilitation and Cognitive Behavioural Interventions 607

suggests that fibromyalgia patients walking at comfortable speed are neurologically walking fast with a correspondingly higher metabolic demand and increased fatigue, and this may explain why fibromyalgia patients readily complain of fatigue in walking at comfortable speed [100]. In summary, identifying and understanding gait abnormalities, and their contributing factors, may assist therapists to more precisely guide their patients towards more efficient muscle recruitment strategies during walking. This will require making the patients aware of what they are doing and how to correct the movements. Aids might be prescribed after careful evaluation and the patient should learn (and comply with) the proper way of using these aids to achieve the desired effect and to avoid secondary side effects. Use of full-length mirrors or video cameras can provide useful feedback to the patient in this task. Successful improvement of gait could lead to more efficient and less tiring walking, less secondary musculoskeletal pain and, ultimately, facilitate the resumption of more functional lifestyles.

It appeared that the key to success is physical activity itself, rather than any specific activity. Other important contributing factors to good outcome are clear and consistent communication and collaboration between the referring physician and therapists, supervision, individual followup and adjustment of the training programme to fit needs and take into account the individual’s predisposition, and characteristics of the social context to enhance compliance [1, 67]. It also needs to be emphasised that in the studies reviewed by Liddle et al., exercise was rarely the sole intervention. In most cases, exercises were either delivered according to behavioural principles [33] or incorporated in more comprehensive rehabilitation programmes where other modalities were employed as well [6]. Liddle et al. therefore cautioned that “the effects of exercise co-interventions must not be overlooked when interpreting these results” [67]. A Cochrane review of exercises for CLBP concluded that there is evidence that exercise/ activity programmes which include a cognitivebehavioural approach are more effective than any exercise alone [111].

Exercise and reactivation Exercise can be defined as any activity which involves the generation of force by the activated muscles. Exercise is often prescribed for preventive, therapeutic, or rehabilitative purposes, but there is a continuing debate about the degree of specificity of prescription required for chronic pain conditions. The major components of an exercise prescription are the type of activity, the frequency of exercise (number of sessions per week), the duration of each exercise session (for strength training the number of sets and repetitions per set are given) and the relative intensity of the effort [52]. Exercises that enhance strength and cardiovascular endurance have been described in the literature for different conditions and should be applicable to patients with pain [27, 102]. The role of exercise in chronic pain conditions has been widely discussed in the context of chronic musculoskeletal disorders, especially painful spinal conditions, arthritic diseases and fibromyalgia. The International Paris Task Force on Back Pain recommended that patients who have CLBP should perform physical, therapeutic, or recreational exercise, keeping in mind that no specific active technique or method is superior to another.

Graded exposure A subgroup of patients with chronic pain appears to have significant activity impairment and disability due to fear-avoidance beliefs and behaviours. Vlaeyen et al. postulated that avoidance of feared activities leads to the maintenance or exacerbation of that fear, similar to the development of a phobia. In a study aimed at reversing these effects through graded exposure (to the feared activities) with a group of CLBP patients with high fear-avoidance beliefs, they found that when the graded exposure approach was compared with similar patients participating in a graded activity programme which explicitly excluded performance of any of their feared activities, those who participated in the graded exposure approach showed improvement in fear of movement/reinjury, pain catastrophising and fear of pain. These interventions included discussion about the benign nature of their chronic pain, the problem of overly alarmist thinking, and the role and impact of fear and avoidance in promoting disability and pain. Patients were encouraged to engage in their feared activities, starting with the least feared and moving on to those they feared more [139].

608 Tak Yi CHUI, Michael K. NICHOLAS

In a second study, De Jong et al. repeated a similar approach with eight patients diagnosed with complex regional pain syndrome (CRPS) Type I. After graded exposure, all patients showed improvement of more than 50% of the scores on functional scales, as well as significant reduction in fear-avoidance beliefs, and positive changes in CRPS-related signs and symptoms. Most interestingly, before the programme, none of the participants believed that graded exposure was a meaningful treatment as they were rated low in the expectancy and credibility ratings [140]. The findings of this study provided clear support for the fear-avoidance model, and indicated that it did not apply only to low back pain [22]. The study also found that brain imaging of treated CRPS-I patients demonstrated a degree of cortical reorganisation with shrinkage of the cortical representation of the effected limb in the primary somatosensory cortex, just as in patients with stroke and post-traumarelated CRPS. The reactivation of the cortical areas subserving the affected limbs suggests that the primary goal of improving function is accompanied by related cortical changes. The evidence from the graded exposure interventions indicates that simply encouraging more general activity is unlikely to be sufficient for restoration of function in those with chronic pain and strong fear-avoidance beliefs. Instead, carefully planned exposure (via performance) to actual feared and avoided activities is essential and must be a focus of treatment as well.

Functional capacity evaluation In patients with chronic pain, measurement of functional capacities of the musculoskeletal system may provide important information for clinical management in assessment, planning for treatment and rehabilitation, and evaluation. Its role in prediction of outcome is less clear. Functional capacity can be assessed by self-reports with standard questionnaires (which are measures of self-perceived ability and function), clinical examinations and standardised functional tests with or without the aid of equipment under controlled environments. Over the past three decades, a battery of tests for measuring functions to assess work-related capability of injured patients have been developed and referred to under “Functional Capacity Evaluation (FCE)”. Currently, there are many marketers of functional capacity evaluation

systems and FCE has been carried out by a variety of personnel, including physiotherapists, occupational therapists, vocational evaluators, physicians, etc., depending on the setting. As the new ICF model has emphasised, functional ability involves a dynamic interaction among bodily functions and structure, ability to perform activities and participation in society, and FCE provides an alternative measurement for deducing work readiness through evaluations at the level of work-related activity and participation in the actual work environment. It also acknowledges that function is influenced not only by injury to bodily structures but also by environmental factors such as the physical or social setting and personal factors such as subject motivation and attitude. Thus, FCE is more accurately viewed as behavioural assessment as opposed to pure physical tests [43]. Functional capacity evaluation is not a standalone test [56]. It is a process involving evaluation of medical, physical status, social and psychological status, job evaluation and an analysis of the findings [57]. The results of FCE are increasingly used by clinicians, employers and benefits adjudicators as a reference for evaluation of the person to perform work and often have legal and occupational consequences [103]. In view of this, it is crucial that the person who refers a client for such assessment, the assessor and personnel who will interpret and use the results for clinical, medico-legal and compensation decisions, should appreciate the limitations of FCE and how it could be used optimally for the particular purpose in question. Psychometrics is a key property to be considered for any scientific measurements. For FCE, content validity would be affected if there were no detailed job analysis and tasks tested were merely extrapolated from job titles [103]. One particular domain of concurrent validity is related to the sincerity of effort or inconsistent performance determinations made during FCE. The sensitivity and specificity of FCE vary significantly in different studies [66]. The likelihood of detecting feigning using this test is very low if feigning is uncommon in the population being tested [43]. As indicated earlier, there are many possible reasons for submaximal effort. They include failure to understand the degree of effort required, anxiety

Functional Rehabilitation and Cognitive Behavioural Interventions 609

related to the test situation, depression, pain intensity, fear-avoidance beliefs, self-perceptions of ability/disability, unconscious or conscious illness behaviour such as exaggeration, or malingering [43, 44, 51]. In a review by Lechner et al. on methods and approaches in detecting sincerity of effort, it was found that none of the measures that examine effort (Waddell’s non-organic signs, descriptions of pain behaviour and symptom magnification, coefficients of variation, correlations between musculoskeletal evaluation and function, grip measurement, and the relationship between heart rate and pain intensity) examined this aspect adequately. None of the approaches was directly correlated to outcome. The author recommended that efforts should be made to identify (as much as possible) and manage any factors that may be contributing to poor performance, especially as mislabelling of patients as being “insincere” is likely to have a detrimental effect on the accuracy of assessment, adequacy of treatment and could cost the individual his/her job [62].

class correlation values, while 11 of the 18 tests (61%) showed an acceptable reliability [9]. Brouwer et al. cautioned that as only 30 out of 100 patients meeting the selection criteria were recruited, the results may have been biased, limiting the reliability of the test in real clinical settings [9].

The predictive validity of FCE is another psychometric property of concern particularly in terms of sustained ability to return to work at the determined work level. Studies have shown that pain level and worker’s compensation status, and amount of time off work are strong predictors for returning to work, while the predictive value of the functional capacity evaluation tests were not consistently so [20, 29, 75]. It also needs to be remembered that functional capacity is only likely to be one factor in determining return to work. The nature of the work and the ability and willingness of the employer to accommodate the injured worker back at work are also potent factors that must be considered [31].

Effects of Compensation and Litigation on Rehabilitation

Intra- and inter-rater reliability are also important considerations with FCE tests [135]. Written and clear guidelines on how to perform the test were shown to improve the inter-rater reliability on determining safe versus unsafe lifting. However, it should be noted that raters’ judgements might be more conservative when there is a high incidence of litigation [38]. The reliability of rater judgements of safe frequency tolerances for work over an 8hour day has not been studied [43]. In a study by Brouwer et al. of the test-retest reliability of all tests of the Isernhagen Work Systems in a sample of patients with CLBP, 15 of the 19 tests (79%) showed an acceptable agreement, based on intra-

Clearly, further research in FCE is required as there are still significant limitations. The validity and reliability in different settings need to be demonstrated and the role of behavioural variables in performance testing have to be better understood. We also need to compare the psychometric properties of FCE versus expert-based (e.g. physician) functional evaluation and to make FCE more userfriendly by shortening the evaluation time. It is also important to differentiate maximal and submaximal efforts and identify the reasons behind and to assess the limitations of predicting “workability”, which is a multidimensional construct, by the single dimension FCE measurements [105].

The literature on the impact of litigation, such as compensation proceedings, for potentially compensable injuries among people with chronic pain has elicited disparate findings and opinions [123]. Earlier descriptive studies suggested that patients applying for or receiving compensation due to injury were often characterised by features such as exaggeration of their pain, excessive anxiety, depression and neuroticism. They were often assumed to be planning to return to work promptly after receiving the verdict of the litigation case [88, 118, 127, 148, 151]. A meta-analysis by Rohling et al. showed that the presence of compensation was related to increased reports of pain and decreased treatment efficacy [106]. Similar findings were reported by another meta-analysis of surgical outcomes, that the presence of compensation is associated with poorer outcomes regardless of type of surgery and country [48]. Most recently, Gabbe et al. using a prospective cohort study, found that patients covered by compensation for transportrelated orthopaedic trauma had worse outcomes than non-compensable patients 12-months after injury [35]. However, other research findings and reviews have failed to prove consistently these effects of compensation status or litigation status

610 Tak Yi CHUI, Michael K. NICHOLAS

on symptom presentation and treatment response [36, 79, 82]. When clinicians encounter patients with compensable injury, there is a dual risk of bias. On the one hand, the clinician might tend to downplay the significance of symptoms [124]. On the other hand, patients might try to promote their symptoms either in response to distress or in an effort to convince physicians of their work incapacity [71], in turn leading physicians either to discount symptom reports [17, 86, 125] or to develop negative stereotypes for these “compensation claimers”. Clinicians might also more readily develop pessimistic expectations regarding treatment outcomes when they know that their patient has a compensation claim [114]. However, patients with or without compensation claims/ litigation often do have similar pain experiences and psychological profiles [81, 82 83]. The “wrestling” between the two parties might result in undesirable physician-patient interactions, which in turn may contribute to iatrogenic disability [69, 76, 121]. Another possible iatrogenic factor is the delay in referral of patients involved in compensation proceedings to multidisciplinary treatment, which has been shown to be effective in this subgroup of chronic pain patients, or offering fewer treatment options, such as surgery [3, 4, 5]. It is worth noting that patients involved in compensation claims for intractable pain have been found to reciprocally hold less confidence in a physician’s diagnosis than those not so involved [124]. The notion of “cured by verdict” was challenged by studies which showed a low return-to-work rate after settlement [84], settlement having no effect on adjustment [41], and no change in symptoms after settlement [99]. Indeed, expectation and beliefs of the patients may affect the outcome rather than compensation status per se [10, 11, 40]. In a prospective study, receipt of compensation and use of a lawyer did not reduce the probability of return-to-work in disabled persons but increased the likelihood of return to work for groups of individuals at higher risk such as those with external locus of control [37]. External health locus of control is thought to be associated with a greater dependency on others for one’s health outcome, and in this context, it may be seen as a dependence on compensation for successful recovery. Higher distress in uncompensated individuals may be caused by their perception that

society (as represented by insurers, employers and even doctors) did not fulfil their responsibilities by denying them needed financial support and treatment for their recovery to which they feel entitled. Meeting this “unwritten contractural agreement” could alleviate the patients’ anger and distress and might help them proceed successfully with rehabilitation [37]. The diathesis-stress model has been used to explain the effect of compensationrelated stress (job inflexibility, stigma, financial hardship, litigation) in pain-related disability and poorer response to treatment apart from that of pain-related stress [24, 89]. Treatment programmes which help patients to address both sources of stress might lead to better outcome [32]. A recent meta-analysis of workplace-based interventions found that when the major stakeholders (employee, employer, health professionals and insurer) work in a collaborative way, the return-to-work outcomes are significantly improved compared with when this doesn’t happen [30]. This suggests that the possible negative influence of a compensation claim can be overcome by these means. Another variable that affects outcome of individual claims is the employment status. Lemstra et al. found that compensation patients still employed responded to treatment as well as patients not pursuing compensation proceedings. Compared with clinic-based programmes, such as rapid and expanded physical therapy programmes, occupationbased management programmes (which focus on injury prevention, minimal clinical intervention, reassurance of a good prognosis, encouragement to resume normal activity as soon as possible, simple exercises, and early return to work on timelimited and monitored, modified or light duties, and are conducted by an independent practitioner) had significant effects on time loss, injury claim incidence, duration and costs [65]. In the US, some researchers have challenged the effectiveness and true cost-benefit ratio in terms of returning to work, claimed by “expensive” multidisciplinary industry in the name of “functional restoration” that has evolved to serve the Workers’ Compensation Insurance paradigm and criticised the underlying motives of the programme providers [46]. Hadler emphasised that effort should be made in providing accommodating workplaces, bestowing compassion and facilitating the “claimants” to cope instead of asking them to go through the “vortex of disability determination” [46]. The issue of disability determination as the basis of future financial

Functional Rehabilitation and Cognitive Behavioural Interventions 611

benefits is an understandable and likely obstacle to recovery. However, it does not automatically follow that multidisciplinary interventions for suitable patients in this group are inappropriate or excessively expensive. There is also the possible cost of not pursuing this course in these cases to be considered. From a review of published studies, Turk concluded that multidisciplinary pain rehabilitation programmes are significantly more cost-effective than spinal cord stimulators, implantable drug delivery systems, conservative care and surgery, even for selected cases [129]. Recent examinations of the return-to-work literature for injured workers have suggested that it is not just the nature of the treatment that needs to be considered but rather how well it is integrated into the return-to-work process (e.g. the linkages between the treatment providers and the workplace) [30]. The insurance system is another important contextual factor which affects the functioning of an individual with chronic pain. It can be to the advantage of insurance companies and private health care organisations to exaggerate the incidence of patient fraud, providing a basis for maintaining strict controls over potentially expensive claims [19]. Conscientious health care providers would be concerned about delivery of optimal care to those in need and the responsibility for cost containment. The dissociation between symptoms and evidence of physical pathology is often a cause of puzzlement. In these circumstances, health care practitioners may be tempted to speculate on a role for psychological mechanisms, including conscious intent. Crag et al. have pointed out the misuse of “pain behaviours”, limitations of “intuition-based strategies” upon specific cues or “red flag” (e.g. behavioural inconsistencies, poor co-operation, inability or refusal to complete testing, particularly severe symptoms, absence of objective test results) in defining malingering [19]. In the medicolegal context, it was warned that clinicians and independent medico-legal examiners might exhibit “malingerophobia”, which is characterised by “an irrational and maladaptive fear of being tricked into providing health care to individuals who masquerade as sick, but either have no illness at all, or have a much less severe one than they claim” [101]. It was argued that “malingering”, the wilful, deliberate, and fraudulent feigning or exaggeration of illness, is a legal finding, and not a clinical or psychiatric diagnosis [85]. More recently, there are concerns that the view of pain

may be diminished and minimised by members of the medical profession, sometimes directly because they have worked for insurance companies who seek such minimisation of suffering of their clients. In order that future research and consensus group recommendations may result in better care and a fairer compensation system, substantial efforts to minimise bias will be required [87]. In the modern society, the optimal treatment and rehabilitation of injured workers requires good communication, up-to-date information and cooperation between multiple parties, e.g. health care providers, the workplace, worker’s compensation boards, insurance companies, regulatory agencies, courts and legal representatives, and welfare and social security systems (where relevant in individual cases). Very often, the interests of different parties are not in line, resulting in delayed and suboptimal management. The “contextual factors” in the contribution of the eventual functioning of injured workers would be even more complex if clinicians have to serve the interests of different parties, in addition to the original call to relieve pain and suffering of patients in their vocation [12]. While such complexity can easily give rise to feelings of hopelessness among providers, ways must be found around these potential obstacles. A recent review explored a range of possibilities that might give rise to at least some basis for optimism [31].

Using Cognitive Behavioural Therapy Methods in Functional Rehabilitation in People with Chronic Pain There is strong evidence that cognitive behavioural pain management programmes can limit the impact of chronic pain on patients and assist them to resume normal functional activities [39, 45, 90, 129]. However, access to these multidisciplinary pain programmes is not always possible due to limited availability and restricted local resources. Accordingly, many of those working in pain clinic or rehabilitation settings are faced with devising modified versions of the programmes described in the literature to address the problems presented by their chronic pain patients. There is good evidence that this can still achieve better results than not applying these principles at all [111, 147].

612 Tak Yi CHUI, Michael K. NICHOLAS

Cognitive behavioural approaches to pain management are based on the evidence that persisting pain (and its associated problems) is best understood within a biopsychosocial framework [130]. As indicated earlier, this requires a thorough evaluation of the medical (biological) aspects of each patient, as well as careful assessment of possible psychological and social/environmental factors that may be contributing to the patient’s difficulties. The assessment findings provide the basis for the cognitive behavioural intervention that may be targeted at multiple levels. At the individual patient’s level, these could include addressing medication use, behaviours/activities, mood and cognitions (thought processes). At the social level, the intervention could address interactions with the patient’s significant others (e.g. workplace, family, other health care providers) and aspects of the patient’s normal environment (e.g. workplace and home duties, daily travel arrangements) [94].

Principles of cognitive behavioural therapy Cognitive behavioural therapy (CBT) is based on a number of empirically developed principles derived from the scientific study of behaviour and cognitions, beginning with researchers like Pavlov and Skinner. Of particular relevance has been the study of learning (conditioning), cognitive processes, social interactions and more recently, applications of interventions based on this literature to mental and physical illnesses in clinical settings [25, 34, 50,146]. Some key principles of CBT are described in Table 38.04. From these principles it can be appreciated that CBT is not a fixed “package” with a standard content like a drug. Instead, it may be more accurately thought of as a set of operating principles which can guide the behaviour of a clinician in his/her interactions with a given patient. The effectiveness of CBT is very operator-dependent. It depends upon how well it is applied and the skills of the health professionals involved. In turn, these depend upon the adequacy of the initial assessment to ensure that as many as possible of the factors contributing to a patient’s presenting problems have been identified for inclusion in the treatment process. The patient also plays an active role in CBT so s/he must be

Table 38.04 Key principles underlying cognitive behavioural therapy with pain patients • A patient’s beliefs about his/her pain condition and its management are likely to influence their behaviour • A patient’s mood is influenced by their beliefs and behaviours • Pain management skills and related beliefs are learned (i.e. able to be changed) • Motivation to change derives from goals that are personally relevant (to the patient) • The patient’s environment can enhance or impede self-management of pain and rehabilitation • Consistent reinforcement of desired behaviours/responses will increase their frequency (and strengthen their durability), but reinforcement of conflicting responses and inconsistent reinforcement will result in less predictable outcomes • The impact of information on a patient’s beliefs and behaviour is influenced by the credibility of the source, its quality and its personal relevance • Maintenance of effective pain selfmanagement by a person in persisting pain requires skills or coping strategies that can be implemented by the person in their own normal environment — skills training in one environment must attend to their application elsewhere.

adequately prepared for the treatment process and motivated to change.

Treatment planning/preparation If a CBT approach is to be implemented alongside other interventions, the treatment providers must consider the timing of their implementation. Thus, if invasive procedures are planned (aimed at pain relief or reduction), it would normally be preferable that these precede the CBT intervention (which is aimed at pain management rather than pain relief ) [95]. The two approaches (pain management and pain relief ) can be applied simultaneously, but this requires selection of the appropriate patient (ideally one who already practises helpful self-management strategies) and careful explanation of the regimen to ensure the patient is adequately prepared, as well as willing and able to play an active role in the processes [97].

Functional Rehabilitation and Cognitive Behavioural Interventions 613

Goal setting Prior to the intervention, the desired outcome goals should be negotiated with the patient to ensure they are relevant to him/her, as well as realistic or appropriate (in the eyes of the health providers). It is preferable that all goals are described terms of observable or measurable activities (e.g. return to normal duties at work, or driving a car for 30 minutes, or sleeping without drugs), rather than less specific entities (e.g. to “be happy”).

Collaboration A key feature of CBT interventions is that all those involved take a consistent approach to the patient. In order to achieve this, all those involved in the rehabilitation process of a patient about to commence a CBT approach must collaborate as much as possible [94, 145]. This should include their being aware of the approach being taken, the expected outcomes (i.e. not pain relief ) and the programme’s expectations of their roles prior to and following the programme. Normally, this would include the patient’s medical carers and family

Reduced activity

Unhelpful beliefs & thoughts

CHRONIC PAIN

Repeated treatment failures

(and any other health care providers involved). Any disagreements between the providers over the planned intervention should be resolved prior to commencement. Any suggestion of dissent may risk a poorer outcome, especially in an ambivalent patient. Collaboration with the patient is also essential as CBT cannot be done to someone, but only with their active involvement. This can be facilitated by the treating doctor (who usually has an established and credible relationship with the patient) spending some time on preparation of the patient for the CBT approach. As CBT represents a shift from a passive, painrelief-first approach (where something is done to the patient, or they are given something for the pain), the shift in focus, and its implications, must be clearly discussed and explained to the patient. In particular, as with any treatment, the use of CBT should not be presented as “the last resort” for those who have failed standard medical interventions (which would risk feelings of abandonment or somehow having “less real” pain). Instead, it may be presented as a

Physical deterioration (Eg. Muscle wasting, joint stiffness)

Feelings of depression, helplessness, frustration, anger

Long-term use of multiple drugs

Loss of job, financial difficulties, family stress

Figure 38.01

Side effects (Eg. Stomach problems, lethargy, constipation)

Reconceptualising the problems of chronic pain.

EXCESSIVE SUFFERING

614 Tak Yi CHUI, Michael K. NICHOLAS

logical next step for dealing with a complex array of problems with no easy answers. It may be combined with other modalities, but the expectations on the patient and his/her role in the process of treatment must be made as clear as possible and any questions they may have should be addressed. It is particularly, important that the patient is aware they will be expected to be trying to learn ways of achieving their goals despite their pain and that the programme will be aimed at assisting them in this. The diagram described in Fig. 38.01 can be used to help the patient make sense of the complex nature of their pain and how different aspects can be simultaneously targeted in treatment.

Re-formulation When preparing a patient for this approach or at the start of the programme a session on “reformulation” or “re-conceptualisation” of the patient’s problem(s) will help him/her to make sense of the treatment [53]. As indicated in Fig. 38.01, this typically involves teasing-out the impact of pain on different aspects of the patient’s lifestyle and consideration of possible interaction effects between features such as reduced activity level and mood. This enables the re-conceptualisation of the problem from the view that “pain was the problem and if it could be resolved all would return to normal” to an appreciation of interaction effects and why attempts to raise activity levels and mood, independently of pain, could be helpful. It can be useful to develop a diagram of this reconceptualisation along the lines of Fig. 38.01 and give this to the patient to take home [93]. The re-formulation of chronic pain for the patient should also include a discussion of the differences between acute and chronic pain as well as between hurt and harm. If patients are expected to have to learn to live with their pain (and to lead as normal a life as possible despite their pain) it is important that they are reassured about the benign nature of chronic pain (even though it often doesn’t feel benign to them).

Format The vast majority of studies of CBT pain management programmes have involved groupbased interventions, where five to 10 patients at a time might participate. This has benefits in terms of cost-efficiency in use of staff, as well as enhancing

the sense of support among the participants. However, if a significant number of participants are hostile and unwilling to seriously participate they can adversely affect the progress of other group members, at least initially. Dealing with such challenging group dynamics requires considerable skills of the staff. An alternative to the group-based approach is to employ an individual approach, where the team members (or a clinical psychologist, physiotherapist, nurse, psychiatrist, pain specialist, or general practitioner alone) work with one patient at a time. This may have benefits in terms of ability to individualise the treatment and flexibility in appointment times and service delivery, but to date there is insufficient evidence to say if the efficacy of this approach is equivalent to the group-based approach.

Skills Considerable knowledge and skills are required to assess and manage persisting pain effectively, especially in complex cases. The International Association for the Study of Pain (IASP) has recommended core curricula for professional education in this area [28]. It should be noted that the assessment and management of pain is not a major feature of most professional training programmes (whether it be in medicine, nursing, physiotherapy, psychology, occupational therapy, etc). Thus, while there is a substantial body of knowledge available, relatively few health professionals are familiar with it. Training and supervision for those new to the area is strongly recommended [94]. While this applies to the use of CBT generally [107], it is still possible for those disciplines with little background in behavioural psychology to learn the fundamental CBT principles and to apply them effectively, especially if adequately supervised initially.

Multidisciplinary team At a minimum, a CBT pain management programme requires a clinical psychologist, physiotherapist and some input from a physician with expertise in pain management. However, the inclusion of an occupational therapist, nurse and rehabilitation adviser provides for fuller coverage of problem areas. In many pain or rehabilitation settings, only some of these disciplines may be represented, so usually some pragmatism is

Functional Rehabilitation and Cognitive Behavioural Interventions 615

required to develop an achievable service according to local resources. Regardless of their composition, the staff must have extensive training in ways of working co-operatively, in an integrated manner lest the effectiveness of the programme becomes suboptimal. A common issue that all programmes must address concerns questions about professional “turf ” and hierarchical decision-making processes. While these are common features or traditions of many health care facilities, they risk undermining collaborative care arrangements. Careful attention to resolving these issues needs to be made by those in charge of such programs [126].

Content To some extent, the content of the CBT programme depends on consideration of which treatment, for which patient and under which conditions [128, 131, 143]. In general, there is evidence that the more disabled, medication-dependent patients are more likely to benefit from more intensive cognitive behavioural pain management programmes (i.e. in the range of 100–120 hours) [45, 47, 152]. However, resources may not permit this level of intensity, so compromises may be needed. Good examples of these from Hong Kong and Malaysia can be found in Nicholas et al. [96]. In less disabled cases (at work, but struggling; taking little medication; only mildly distressed) briefer cognitive behavioural pain management programmes are effective (e.g. six 2-hour sessions or possibly 12 1-hour sessions) [68, 74]. Typical features of a CBT pain management programme include: goal setting, education about

pain, applied relaxation training, training in identifying and challenging unhelpful cognitions (beliefs, thought processes), learning more effective problem-solving and pain management strategies (e.g. activity pacing, daily planning); programmed exercise and systematic encouragement of activities to address avoidance behaviours and to regain confidence in functioning despite pain; and structured medication withdrawal [98]. A treatment manual (for the patient) describing the pain management skills and how to use them, plus pain education material can help promote acquisition of skills and maintenance of gains. One example of this is the self-help book which has recently been translated by pain clinicians in Hong Kong into Chinese [13, 98].

Planning for maintenance after pain management As the pain under discussion is chronic, it is likely to not only persist but also to fluctuate. Accordingly, the risk of relapse into disability is high. This may be countered by a number of strategies, ideally in collaboration with the patients’ other carers or significant others. These include: the practice of strategies to deal with high-risk situations (e.g. periods of flare-up in pain severity, set-backs in attempts to return to work); offers of further investigations or passive treatments; preparation of the patient’s normal/ family doctor in ongoing management strategies aimed at maintaining the self-management approach by the patient; and assistance in rehabilitation planning [92, 133].

References 1. 2.

3. 4.

Abenhaim L, Rossignol M, Valat J-P, et al. The role of activity in the therapeutic management of back pain: Report of the International Paris Task Force on Back Pain. Spine 2000;25:15–335. Arkela-Kautiainen M, Haapasaari J, Kautiainen H, et al. Functioning and preferences for improvement of health among patients with juvenile idiopathic arthritis in early adulthood using the WHO ICF model. J Rheumatol 2006;33(7):1369– 76. Atlas SJ. Point of view: Predictors of outcome in patients with chronic back pain and low-grade spondylolisthesis. Spine 1997;22(17):2035. Atlas SJ, Chang Y, Kammann E, et al. Long-term disability and return to work among patients who have a herniated lumbar disc: The effect of disability compensation. J Bone Joint Surg Am 2000;82(1):4–15.

616 Tak Yi CHUI, Michael K. NICHOLAS

5.

6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36.

Becker N, Hojsted J, Sjogren P, et al. Sociodemographic predictors of treatment outcome in chronic non-malignant pain patients. Do patients receiving or applying for disability pension benefit from multidisciplinary pain treatment? Pain 1998;77:279–87. Bendix T, Bendix A, Labriola M, et al. Functional restoration versus outpatient physical training in chronic low back pain: A randomized comparative study. Spine 2000;25(19):2494–500. Blyth FM, March LM, Brnabic AJM, et al. Chronic pain in Australia: A prevalence study. Pain 2001;89:127–34. Bortz II WM. The disuse syndrome. West J Med 1984;141(5):691–4. Brouwer S, Reneman MF, Dijkstra PU, et al. Test-retest reliability of the Isernhagen Work Systems Functional Capacity Evaluation in patients with chronic low back pain. J Occup Rehab 2003;13(4):207–18. Buchbinder R, Jolley D, Wyatt M. Population based intervention to change back pain beliefs and disability: Three part evaluation. Bone Muscle Joint 2001;322(7301):1516–20. Burns JW, Sherman ML, Devine J, et al. Association between workers’ compensation and outcome following multidisciplinary treatment for chronic pain: Roles of mediators and moderators. Clin J Pain 1995;11:49–102. Cassell EJ. The Nature of Suffering and the Goals of Medicine, 2nd edn. Oxford: Oxford University Press, 2004:29–75. Chen PP, Ma M, eds. Manage Your Pain (Chinese Edition). Hong Kong: Chinese University Press, 2006. Cieza A, Brockow T, Ewert T, et al. Linking health-status measurements to the international classification of functioning, disability and health. J Rehabil Med 2002;34(5):205–10. Cieza A, Stucki G. New approaches to understanding the impact of musculoskeletal conditions. Best Pract Res Clin Rheumatol 2004;18(2):141–54. Cieza A, Stucki G, Weigl M, et al. ICF Core Sets for low back pain. J Rehabil Med 2004b;(44 Suppl):69–74. Clayer JR, Bookless-Pratz CL, Ross MW. The evaluation of illness behaviour and exaggeration of disability. Br J Psychiatry 1986;148:296–9. Cocchiarella L, Andersson GBJ. Guides to the Evaluation of Permanent Impairment. Chicago: American Medical Association Press, 2002:509. Craig KD, Badali MA. Introduction to the special series on pain deception and malingering. Clin J Pain 2004;20(6):377– 82. Cutler RB, Fishbain DA, Steele-Rosomoff R, et al. Relationships between functional capacity measures and baseline psychological measures in chronic pain patients. J Occup Rehab 2003;13(4):249–58. Dahl TH. International classification of functioning, disability and health: An introduction and discussion of its potential impact on rehabilitation services and research. J Rehabil Med 2002;34(5):201–4. de Jong JR, Vlaeyen JW, Onghena P, et al. Reduction of pain-related fear in complex regional pain syndrome type I: The application of graded exposure in vivo. Pain 2005;116(3):264–75. Donnelly C, Carswell A. Individualized outcome measures: A review of the literature. Can J Occup Ther 2002;69(2):84– 94. Dworkin RH, Banks SM. A vulnerability-diathesis-stress model of chronic pain: Herpes zoster and the development of postherpetic neuralgia. In Gatchel RJ, Turk DE, eds. Psychosocial Factors in Pain: Critical Perspectives. New York: Guilford Press, 1999:247–69. Eccleston C. Role of psychology in pain management. Br J Anaesth 2001;87(1):144–52. Erickson RP, McPhee MC. Clinical evaluation. In Delisa JA, ed. Rehabilitation Medicine. Principles and Practice, 3rd edn. Philadelphia, New York: Lippincott-Raven, 1998:61–108. Feigenbaum MS, Pollock ML. Prescription of resistance training for health and disease. Med Sci Sports Exerc 1999;31(1):38–45. Fields HL, ed. Core Curriculum for Professional Education in Pain, 2nd edn. Seattle: IASP Press, 1995. Fishbain DA, Cutler RB, Rosomoff H, et al. Validity of the dictionary of occupational titles residual functional capacity battery. Clin J Pain 1999;15(2):102–10. Franche RL, Cullen K, Clarke J, et al. Workplace-based return-to-work interventions: A systematic review of the quantitative literature. J Occup Rehab 2005a;15(4):607–31. Franche RL, Baril R, Shaw W, et al. Workplace-based return-to-work interventions: Optimizing the role of stakeholders in implementation and research. J Occup Rehab 2005b;15(4):525–42. Frank J, Sinclair S, Hogg-Johnson S, et al. Preventing disability from work-related low-back pain. Can J Med Assoc 1998;158(12):1625–31. Frost H, Lamb SE, Klaber Moffett JA, et al. A fitness programme for patients with chronic low back pain: 2-year followup of a randomised controlled trial. Pain 1998;75:273–9. Fordyce WE. Behavioural Methods for Chronic Pain and Illness. St Louis: C. V. Mosby, 1976. Gabbe BJ, Cameron PA, Williamson OD, et al. The relationship between compensable status and long-term patient outcomes following orthopaedic trauma. Med J Aust 2007;187(1):14–7. Gallagher RM, Rauh V, Haugh LD, et al. Determinants of return-to-work among low back pain patients. Pain 1989;39(1):55–67.

Functional Rehabilitation and Cognitive Behavioural Interventions 617

37. Gallagher RM, Williams RA, Skelly J, et al. Worker’s compensation and return-to-work in low back pain. Pain 1995;61:299–307. 38. Gardener L, McKenna K. Reliability of occupational therapists in determining safe, maximal lifting capacity. Aust Occup Therap J 1999;46(3):110–9. 39. Gatchel RJ, Okifuji A. Evidence-based scientific data cost-effectiveness of comprehensive nonmalignant pain. J Pain 2006;7(11):779–93. 40. Gatchel RJ, Polatin PB, Mayer TG. The dominant role of psychosocial risk factors in the development of chronic low back pain disability. Spine 1995;20:2702–9. 41. Greenough CG, Fraser RD. The effects of compensation on recovery from low-back injury. Spine 1989;14:947–55. 42. Gray DB, Hendershot GE. The ICIDH-2: Developments for a new era of outcomes research. Arch Phys Med Rehabil 2000;81(12 Suppl 2):S10–4. 43. Gross DP. Measurement properties of performance — based assessment of functional capacity. J Occup Rehab 2004;14(3):165–74. 44. Gross DP, Battié MC. Factors influencing results of functional capacity evaluations in workers’ compensation on claimants with low back pain. Phys Ther 2005;85(4):315–22. 45. Guzman J, Esmail R, Karjalainen K, et al. Multidisciplinary rehabilitation for chronic low back pain: Systematic review. BMJ 2001;322:1511–6. 46. Hadler NM. The vortex of disability determination. In Hadler NM. Occupational Musculoskeletal Disorders, 3rd edn. Philadelphia Lippincott Williams & Wilkins, 2005:298–321. 47. Haldorsen EM, Grasdal AL, Skouen JS, et al. Is there a right treatment for a particular patient group? Comparison of ordinary treatment, light multidisciplinary treatment, and extensive multidisciplinary treatment for long-term sicklisted employees with musculoskeletal pain. Pain 2002;95:49–63. 48. Harris I, Mulford J, Solomon M, et al. Association between compensation status and outcome after surgery: A metaanalysis. JAMA 2005;293(13):1644–52. 49. Hasenbring M, Marienfeld G, Kuhlendahl D, et al. Risk factors of chronicity in lumbar disc patients: A prospective investigation of biologic, psychological, and social predictors of therapy outcome. Spine 1994;19(24):2759–65. 50. Hawton K, Salkovskis PM, Kirk J, Clark DM, eds. Cognitive Behaviour Therapy for Psychiatric Problems: A Practical Guide. Oxford: Oxford Medical Publications, 1989. 51. Hirsh G, Beach G, Cooke C, et al. Relationship between performance on lumbar dynamometry and Waddell score in a population with low-back pain. Spine 1991;16(9):1039–43 52. Hoffmann MD, Sheldahl LM, Kraemer WJ. Therapeutic exercise. In Delisa JA, ed. Rehabilitation Medicine. Principles and Practice, 3rd edn. New Jork: Lippincott-Raven, 1998:697–743. 53. Holzman AD, Turk DC, Kerns RD. The cognitive-behavioral approach to the management of chronic pain. In Holzman AD, Turk DC, eds. Pain Management: A Handbook of Psychological Treatment Approaches. New York: Pergamon Press, 1986:31–50. 54. International Classification of Functioning, Disability and Health (ICF) Introduction. http://www3.who.int/icf/. 55. Keefe FJ, Hill RW. An objective approach to quantifying pain behavior and gait patterns in low back pain patients. Pain 1985;21(2):153–61. 56. King PM, Tuckwell N, Barrett T. A critical review of functional capacity evaluations. Phys Ther 1998;78(8):852–66. 57. Kornblau BL, Ito M, Kasyan-Itzkowitz P. Functional capacity evaluations. In Boswell MV, Eliot Cole B, eds. Weiner’s Pain Management: A Practical Guide for Clinicians, 7th edn. Boca Raton: CRC Press, 2006:589–601. 58. Kremer EF, Block A, Gaylor MS. Behavioral approaches to treatment of chronic pain: The inaccuracy of patient selfreport measures. Arch Phys Med Rehabil 1981;62(4):188–91. 59. Kuijer W, Brouwer S, Preuper HR, et al. Work status and chronic low back pain: Exploring the International Classification of Functioning, Disability and Health. Disabil Rehabil 2006;28(6):379–88. 60. Lamoth CJ, Meijer OG, Daffertshofer A, et al. Effects of chronic low back pain on trunk coordination and back muscle activity during walking changes in motor control. Eur Spine J 2006;15(1):23–40. 61. Lanser P, Gesell S. Pain management: The fifth vital sign. Health Benchmarks 2001;8(6):68–70. 62. Lechner DE, Bradbury SF, Bradley LA. Detecting sincerity of effect: A summary of methods and approaches. Phys Ther 1998;78(8):867–88. 63. Lee CE, Simmonds MJ, Novy DM, et al. Physical function in patients with cancer: Psychometric characteristics and clinical usefulness of a physical performance test battery. J Pain Symptom Manage 2002;24(4):404–14. 64. Lee CE, Simmonds MJ, Novy DM, et al. Self-reports and clinician-measured physical function among patients with low back pain: A comparison. Arch Phys Med Rehabil 2001;82(2):227–31. 65. Lemstra M, Olszynski WP. The effectiveness of standard care, early intervention, and occupational management in workers’ compensation claims. Spine 2004;29(14):1573–9. 66. Lemstra M, Olszynski WP, Enright W. The sensitivity and specificity of functional capacity evaluations in determining maximal effort: A randomized trial. Spine 2004;29(9):953–9.

618 Tak Yi CHUI, Michael K. NICHOLAS

67. Liddle SD, Baxter GD, Gracey JH. Exercise and chronic low back pain: What works? Pain 2004;107:176–90. 68. Linton SJ, Andersson T. Can chronic disability be prevented? A randomized trial of a cognitive-behavioral intervention and two forms of information for spinal pain patients. Spine 2000;25:2825–31. 69. Loeser JD, Sullivan M. Disability in the chronic low back pain patient may be iatrogenic. Pain Forum 1995;4:114– 21. 70. Lund JP, Donga R, Widmer CG, et al. The pain-adaptation model: A discussion of the relationship between chronic musculoskeletal pain and motor activity. Can J Physiol Pharmacol 1991;69(5):683–94. 71. MacLeod FK, LaChapelle DL, Hadjistavropoulos T, et al. The effect of disability claimants’ coping styles on judgements of pain, disability, and compensation: A vignette study. Rehabil Psychol 2001;46:417–35. 72. Main CJ, Watson PJ. Guarded movements: development of chronicity. J Musculoskelet Pain 1996;4(4):163–70. 73. Mannion AF, Junge A, Taimela S, et al. Active therapy of chronic low back pain: Part 3. Factors influencing self-rated disability and its change following therapy. Spine 2001;26(8):920–9. 74. Marhold C, Linton SJ, Melin L. A cognitive-behavioral return-to-work program: Effects on pain patients with a history of long-term versus short-term sick leave. Pain 2001;91:155–63. 75. Matheson LN, Isernhagen SJ, Hart DL. Relationships among lifting ability, grip force, and return to work. Phys Ther 2002;82(3):249–56. 76. May C, Doyle H, Chew-Graham C. Medical knowledge and the intractable patient: The case of chronic low back pain. Soc Sci Med 1999;48:523–34. 77. Mayer TG, Gatchel RJ. Functional Restoration for Spinal Disorders: The Sports Medicine Approach. Philadelphia: Lea & Febiger, 1988. 78. Mayer TG, Smith SS, Keeley J, et al. Quantification of lumbar function. Part 2: Sagittal plane trunk strength in chronic low-back pain patients. Spine 1985;10(8):765–72. 79. Mayou R. Accident neurosis revisited. Br J Psychiatry 1996;168:399–403. 80. McPeak LA. Psysiatric history and examination. In Braddom RL, ed. Physical Medicine & Rehabilitation, 2nd edn. Philadelphia: Saunders, 2000:3–45. 81. Melzack R, Katz J, Jeans ME. The role of compensation in chronic pain: Analysis using a new method of scoring the McGill Pain Questionnaire. Pain 1985;23:101–12. 82. Mendelson G. Compensation. Pain complaints and psychological disturbance. Pain 1984;20:169–77. 83. Mendelson G. Chronic pain and compensation: A review. J Pain Symptom Manage 1986;1:135–44. 84. Mendelson G. Compensation neurosis revisited: Outcome studies of the effects of litigation. J Psychosom Res 1995;39:695–706. 85. Mendelson G, Mendelson D. Malingering pain in the medico-legal context. Clin J Pain 2004;20(6):423–32. 86. Merskey H, Teasell RW. The disparagement of pain: Social influences on medical thinking. Pain Res Manage 2000;5:259– 70. 87. Merskey H, Teasell RW. Problems with insurance-based research on chronic pain. Med Clin N Am 2007;91:31–43. 88. Miller H. Accident neurosis. Br Med J 1961;1(5230):919–25. 89. Monroe SM, Simons AD. Diathesis-stress theories in the context of life stress research: Implications of the depressive disorders. Psychol Bull 1991;110:406–25. 90. Morley S, Eccleston C, Williams A. Systematic review and meta-analysis of randomised controlled trials of cognitive behavioural therapy for chronic pain in adults, excluding headache. Pain 1999;80:1–13. 91. Moseley GL, Hodges PW, Wittink H, et al. Deconditioning in patients with chronic low back pain. Fact or Fiction? Spine 2000;25(17):2221–8. 92. Nicholas MK. Compliance: A barrier to occupational rehabilitation? J Occup Rehab 1995;5(4):271–82. 93. Nicholas MK. Theory and practice of cognitive-behavioral programs. In Campbell JN, ed. Pain 1996 — An Updated Review. Seattle: IASP Press, 1996:297–304. 94. Nicholas MK. Reducing disability in injured workers: The importance of collaborative management. In Linton SJ, ed. New Avenues for the Prevention of Chronic Musculoskeletal Pain and Disability, Pain Research and Clinical Management, Vol 12. Amsterdam Elsevier Science BV 2002:33–46. 95. Nicholas MK. When to refer to a pain clinic. Best Pract Res Clin Rh 2004;18 (4):613–29. 96. Nicholas MK, Cardosa M, Chen PP. Developing multidisciplinary cognitive-behavioural pain management programs in Asia. In Flor H, Kalso E, Dostrovsky OJ, eds. Proceedings of the 11th World Congress on Pain. Seattle: IASP Press, 2006a:773–87. 97. Nicholas MK, Molloy AR, Brooker C. Using opioids with persisting, noncancer pain: A biopsychosocial perspective. Clin J Pain 2006b;22(2):137–46. 98. Nicholas MK, Molloy AM, Tonkin L, et al. Manage Your Pain. Sydney: ABC Books, 2000. 99. Norris SH, Watt I. The prognosis of neck injuries resulting from rear-end vehicle collisions. J Bone Joint Surg Br 1983;65:608–11. 100. Pierrynowski MR, Tiidus PM, Galea V. Women with fibromyalgia walk with an altered muscle synergy. Gait Posture 2005;22(3):210–8.

Functional Rehabilitation and Cognitive Behavioural Interventions 619

101. Pilowsky I. Malingerophobia. Med J Aust 1985;143(12-13):571–2. 102. Pollock ML, Gaesser GA, Butcher JD, et al. ACSM Position Stand: The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults. Med Sci Sports Exerc 1998;30(6):975–91. 103. Pransky GS, Dempsey PG. Practical aspects of functional capacity evaluations. J Occup Rehab 2004;14(3):217–29. 104. Protas EJ, Mayer TG, Dersh J, et al. Relevance of aerobic capacity measurements in the treatment of chronic workrelated spinal disorders. Spine 2004;29(19):2158–66. 105. Reneman MF, Dijkstra PU. Introduction to the special issue on functional capacity evaluations: From expert based to evidence based. J Occup Rehab 2003;13(4):203–6. 106. Rohling ML, Binder LM, Langhinrichsen-Rohling J. Money matters: A meta-analytic review of the association between financial compensation and the experience and treatment of chronic pain. Health Psycho 1995;14(6):537–47. 107. Roth A, Fonagy P. What Works for Whom? A Critical Review of Psychotherapy Research, 2nd edn. New York: The Guilford Press, 2005. 108. Schasfoort FC, Bussmann JB, Martens WL, et al. Objective measurement of upper limb activity and mobility during everyday behavior using ambulatory accelerometry: The upper limb activity monitor. Behav Res Methods 2006;38(3):439– 46. 109. Schenk P, Klipstein A, Spillmann S, et al. The role of back muscle endurance, maximum force, balance and trunk rotation control regarding lifting capacity. Eur J Appl Physiol 2006;96:146–56. 110. Scheuringer M, Stucki G, Huber EO, et al. ICF Core Set for patients with musculoskeletal conditions in early postacute rehabilitation facilities. Disabil Rehabil 2005;27(7-8):405–10. 111. Schonstein E, Kenny DT, Keating J, et al. Work conditioning, work hardening and functional restoration for workers with back and neck pain. Cochrane Database Syst Rev 2003;(1):CD001822. 112. Sigl T, Cieza A, Brockow T, et al. Content comparison of low back pain-specific measures based on the International Classification of Functioning, Disability and Health (ICF). Clin J Pain 2006;22(2):147–53. 113. Simmonds MJ. The effect of pain and illness on movement: Assessment methods and their meanings. In Giamberadino MA, ed. Pain 2002 — An Updated Review: Refresher Course Syllabus. Seattle: IASP press, 2002:179–87. 114. Simmonds MJ, Kumar S. Does knowledge of a patient’s workers’ compensation status influence clinical judgements? J Occup Rehabil 1996;6:93–107. 115. Simmonds MJ, Olson SL, Jones S, et al. Psychometric characteristics and clinical usefulness of physical performance tests in patients with low back pain. Spine 1998;23(22):2412–21. 116. Sletten CD. Outcome measurement in chronic pain. In Rice ASE, Warfield CA, Justins D, Eccleston E, eds. Clinical Pain Management, 4-volume set. London: Arnold, 2002:145–53. 117. Smeets RJ, Hijdra HJ, Kester AD, et al. The usability of six physical performance tasks in a rehabilitation population with chronic low back pain. Clin Rehabil 2006;20(11):989–97. 118. Sternbach RA, Wolf SR, Murphy RW, et al. Traits of pain patients: the low back “loser”. Psychosomatics 1973;14(4)226– 9. 119. Stratford PW, Gill C, Westaway M, et al. Assessing disability and change in individual patients: A report of a patientspecific measure. Physiother Can 1995;47:258–63. 120. Stucki G, Grimby G. Applying the ICF in medicine. J Rehabil Med 2004;(44 Suppl):5–6. 121. Sullivan MD, Loeser JD. The diagnosis of disability: Treating and rating disability in a pain clinic. Arch Intern Med 1992;152:1829–35. 122. Sullivan M. Exaggerated Pain Behavior: By What Standard? Clin J Pain 2004;20(6):433–9. 123. Tait RC. Compensation claims for chronic pain: Effects on evaluation and treatment. In Dworkin RH, Breitbart WS, eds. Psychosocial Aspects of Pain: A Handbook for Health Care Providers. Progress in Pain Research and Management, Vol 27. Seattle: IASP Press, 2004:547–69. 124. Tait RC, Margolis RB, Krause SJ, et al. Compensation status and symptoms reported by patients with chronic pain. Arch Phys Med Rehabil 1998;69:1027–9. 125. Tarasuk VS, Eakin JM. The problem of legitimacy in the experience of work-related back injury. Qual Health Res 1995;5:204–21. 126. The Pain Society (of UK and Ireland). Desirable Criteria for Pain Management Programmes (1997). Document http:// www.painsociety.org/pdf/desirabl.pdf. 127. Thompson G.N. Post-traumatic psychoneurosis: A statistical survey. Am J Psychiat 1965;121:1043–8. 128. Turk DC. Customizing treatment for chronic pain patients: Who, what, and why. Clin J Pain 1990;6(4):255–70. 129. Turk DC. Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain. Clin J Pain 2002;18:355–65. 130. Turk DC. Cognitive-behavioural approach to the treatment of chronic pain patients. Pain Med 2003;28:73–9. 131. Turk DC. The potential of treatment matching for subgroups of patients with chronic pain: Lumping versus splitting. Clin J Pain 2005;21:44–55.

620 Tak Yi CHUI, Michael K. NICHOLAS

132. Turk DC, Burwinkle TM. Assessment of chronic pain in rehabilitation: Outcomes measures in clinical trials and clinical practices. Rehabil Psychol 2005;50(1):56–64. 133. Turk DC, Rudy TE. Neglected topics in the treatment of chronic pain patients — relapse, noncompliance and adherence enhancement. Pain 1991;44:5–28. 134. van den Berg-Emons RJ, Schasfoort FC, de Vos LA, et al. Impact of chronic pain on everyday physical activity. Eur J Pain [In press] 2006. 135. Velozo CA. Work evaluations: Critique of the state of the art of functional assessment of work. Am J Occup Ther 1993;47(3):203–9. 136. Verbunt JA, Seelen HA, Vlaeyen JW, et al. Pain-related factors contributing to muscle inhibition in patients with chronic low back pain, an experimental investigation based on superimposed electrical stimulation. Clin J Pain 2005;21(3):232–40. 137. Verbunt JA, Sieben JM, Seelen HAM, et al. Decline in physical activity, disability and pain-related fear in sub-acute low back pain. Euro J Pain 2005;9:417–25. 138. Verhoef J, Toussaint PJ, Zwetsloot-Schonk JH, et al. Effectiveness of the introduction of an International Classification of Functioning, Disability and Health-based rehabilitation tool in multidisciplinary team care in patients with rheumatoid arthritis. Arthritis Rheum 2007;57(2):240–8. 139. Vlaeyen JWS, de Jong J, Geilen M, et al. Graded exposure in vivo in the treatment of pain-related fear: A replicated single-case experimental design in four patients with chronic low back pain. Behav Res Ther 2001;39:151–66. 140. Vlaeyen JWS, de Jong J, Geilen M, et al. The treatment of fear of movement/(re)injury in chronic low back pain: Further evidence on the effectiveness of exposure in vivo. Clin J Pain 2002;18:251–61. 141. Vlaeyen JWS, Kole-Snijders AMJ, Rotteveel A, et al. The role of fear of movement/(re)injury in pain disability. J Occup Rehab 1995;5:235–52. 142. Vlaeyen JWS, Linton SJ. Fear-avoidance and its consequences in chronic musculoskeletal pain: A state of the art. Pain 2000;85(3):317–32. 143. Vlaeyen JWS, Morley S. Cognitive-behavioral treatments for chronic pain: What works for whom? Clin J Pain 2005;21:1–8. 144. Vogt L, Pfeifer K, Portscher M, et al. Influences of non-specific low back pain on three-dimensional lumbar spine kinematics in locomotion. Spine 2001;26(17):1910–9. 145. Von Korff M. Collaborative care. Ann Intern Med 1997;127:1097–102. 146. Von Korff M, Russell EG, Sharpe M. Organising care for chronic illness. BMJ 2002;325:92–4. 147. Waddell G, Burton K. Evidence review. In Carter JT, Birrell LN, eds. Occupational Health Guidelines for the Management of Low Back Pain at Work — Principal Recommendations. London: Faculty of Occupational Medicine, 2000. 148. Weighill VE. “Compensation neurosis”: A review of the literature. J Psychosom Res 1983;27(2):97–104. 149. Weigl M, Cieza A, Kostanjsek N, et al. The ICF comprehensively covers the spectrum of health problems encountered by health professionals in patients with musculoskeletal conditions. Rheumatology 2006;45(10):1247–54. 150. Weigl M, Cieza A, Cantista P, et al. Physical disability due to musculoskeletal conditions. Best Pract Res Clin Rh 2007;21(1):167–90. 151. White AW. Low back pain in men receiving workmen’s compensation. Can Med Assoc J 1966;95(2):50–6. 152. Williams AC de C, Nicholas MK, Richardson PH, et al. Generalizing from a controlled trial: The effects of patient preference versus randomization on the outcome of inpatient versus outpatient chronic pain management. Pain 1999;83:57–65. 153. Williams, AC de C. Assessing chronic pain and its impact. In Dworkin RH, Breitbart WS, eds. Psychosocial Aspects of Pain: A handbook for Health Care Providers. Progress in Pain Research and Management, Vol 27. Seattle: IASP Press, 2004:97–116. 154. Wittink H, Hoskins MT, Wagner A, et al. Deconditioning in patients with chronic low back pain: Fact or fiction? Spine 2000;25(17):2221–8.

Index 5-hydroxytryptophan 164, 247 5-hydroxytryptophan (5HT) 164 5-lipoxygenase (5-LX) pathway (leukotrienes) 373 Abbey pain scale 301 abnormal illness behaviour 15 abortive treatment (migraine) 164 ABPI see ankle brachial pulse index absolute risk reduction (ARR) 67, 69 acceptance 590 acceptance and commitment therapy (ACT) 594 acceptance of persisting pain 14 accessory movement, joints 563 acculturation 57 Achilles tendonitis 268, 270 activities of daily living 23, 34, 40, 136, 138, 226, 254, 302, 383, 484, 539, 605 acupoints 549 acupuncture 10, 56, 116, 175, 194, 202, 242, 278, 547 acupuncture like TENS 303 acupuncture nomenclature 550 acupuncture, ear 557 acute gouty arthritis 266 acute neuropathic pain 96 acute pain experience 93 acute pain management, principles of 95 acute pain service 95 acute pain, adverse effect 93 acute pancreatitis 289 adalimumab 263 addiction 102, 141, 173, 305, 343, 356, 475 adjuvant agent 93, 106, 136, 140, 165, 185, 278, 282, 305, 339, 370, 394, 474, 530 adjuvant analgesics, older persons 305 ADL see activities of daily living adrenalin, intrathecal 106 advance directive 85 alfentanil 102, 104, 112, 114, 231 allesthesia 149 allodynia 5, 36, 145, 161, 192, 222, 236, 329 allopurinol 267 alpha-2-adrenoceptor agonist 6, 106, 144, 147, 242, 323, 399, 474, 477 alpha-2-delta subunit of spinal N-type Ca2+ channels 6, 144, 385 alprazolam 394 alternative medicine 547 alvimopan 140, 348, 351 American College of Rheumatology revised classification criteria for rheumatoid arthritis 260

American Society of Clinical Oncology (ASCO) 145 amino-3-hydroxy-5-methyl-4-isoxazolepropionate see AMPA amitriptyline 144, 166, 241, 278, 314, 323, 379, 381 AMPA 1 AMPA receptor 5, 396 amplitude, pulse width and rates 504 anaesthesia dolorosa 190, 236, 240, 513 Analgesic Ladder, WHO 136, 140, 142, 281, 287, 289 anger 41, 137, 573, 582, 592, 613 ankle brachial pulse index 279 ankylosing spondylitis 264, 467 ankylosing spondylitis and spondyloarthritis, management of 265 ankylosing spondylitis, clinical manifestation 264 ankylosing spondylitis, epidemiology 264 ankylosing spondylitis, extra-articular manifestations 264 ankylosing spondylitis, prevalence 264 anorexia 135, 138, 174, 261, 285, 382, 394, 543 anterolateral cordotomy 148, 511, 516 antibodies to cyclic citrullinated peptide 262 anticonvulsant 107, 114, 141, 169, 184, 240, 330, 379, 384 antidepressant 102, 141, 145, 170, 215, 229, 247, 278, 293, 305, 315, 379, 545 antihistamines 323, 350, 400, 543 anxiolytic 114, 165, 323, 486, 542 aplastic anemia, carbamazepine 385 APS see acute pain service arachidonic acid 1, 3, 4, 367, 378, 460 arachidonic acid cascade 368, 378 arteriosclerosis obliterans 279 arthritis and rheumatic diseases, classification of 254 Ashi points 551, 556 aspirin 102, 141, 165, 167, 281, 304, 317, 367, 378 assertiveness training 577 associated biological consequences 38 associated social consequences 38 atenolol 166, 169 attentional fixation 583, 585 attentional fixation on pain and distress 585 attentional processes 13, 15 atypical acupuncture 549 atypical facial pain 193 aura 161, 163 autonomy, respect for 82 axial pain 502 axillary artery 420, 426 axillary sweating 449, 450

622 Index

azathioprine

262

back pain 13, 42, 50, 52, 111, 207, 253, 279, 305, 342, 370, 383, 395, 412, 459, 484, 531, 555, 563, 574, 602 baclofen 145, 173, 185, 396, 478, 519 baclofen, intrathecal 478 bamboo spine 265 basal thalamotomy 518 BDI see Beck Depression Inventory Beck Depression Inventory 39, 74 behavioural and physiological measures 96 behavioural avoidance 583, 594 beliefs, older person’s 300, 302 beneficence 82, 542 benign abdominal pain, role of coeliac plexus block 444, 446 benzodiazepine 114, 145, 169, 341, 387, 394, 544 beyond diagnosis 589 bias 50 bioavailability 99, 185, 315, 353, 354, 359 biochemical selectivity 369 bioethics 81 biological mechanism 53 biological pain contributors 36 biomechanical approach 576 biomedical model of disease 221 biopsychosocial framework 226, 228, 230, 601 biopsychosocial matrix 222 biopsychosocial model, assessment and treatment of disease 32, 327, 328 biopsychosocial model, clinical implication 16 biopsychosocial models of pain 14, 32, 54, 114, 327, 328, 340, 561, 565, 612 Birch, Felt and Lytle’s classification, for acupuncture 549 bisphosphonate 145, 246, 265, 393, 400, 543 BJD see Bone and Joint Decade blepharospasm 395 blinding, clinical research 72 Bone and Joint Decade (BJD) 253, 268 BOTOX see botulinium toxin type A botulinium toxin type A (BOTOX) 170, 395 Bouchard’s nodes 258 BPI see Brief Pain Inventory BPI see Wisconsin Brief Pain Inventory brachial plexus 119, 240, 318, 411, 420, 421, 516, 534 brachial plexus block 322, 420, 423 brachial plexus block, axillary approach 322, 422, 427 brachial plexus block, Infraclavicular approach 421, 422, 425 brachial plexus block, Interscalene approach 322, 421, 423, 424 brachial plexus block, supraclavicular approach 422, 425, 426 brachial plexus block, ultrasound guided axillary approach 427 brachial plexus block, ultrasound guided infraclavicular approach 425

brachial plexus block, ultrasound guided Interscalene approach 424 brachial plexus block, ultrasound guided supraclavicular approach 425 brachial plexus, branches 420, 421 brachial plexus, division 420 brachial plexus, root 420, 421, 429 brachial plexus, trunk 420, 425, 426, 441 brain imaging 6, 31, 46, 518, 608 brain metastases 524, 532, 542 breakthrough pain 86, 140, 143, 324, 341, 353, 480, 506 breast feeding, Casarean section 117 bretylium 246, 412 Brief Pain Inventory 19, 23, 39, 52, 74, 301, 383 buccal, analgesic administration 99, 316, 353 Buerger’s disease 279 bupivacaine 105, 110, 116, 147, 171, 314, 320, 380, 407, 429, 463, 473, 489 buprenorphine 102, 104, 143, 281, 290, 305, 348, 487 burn, pain relief in 113, 323 butorphanol 102, 104, 143, 165 cachexia 134, 137, 138, 150, 277, 538, 541, 543 Caesarean section 117 calcium channel blocker 166, 169, 283 calf muscle ischemia 443 Canadian Occupational Performance Measure 575 cancer pain control, principles of prescription 140 cancer pain relief 83, 138, 139 cancer pain, abdominal 444 cancer pain, assessment and evaluation of 132, 137 cancer pain, bone 132 cancer pain, epidemiology 131 cancer, epidemiology 131 cannabinoid receptor 398 cannabinoids 398 capsaicin 42, 45, 173, 225, 241, 278, 393, 400 carbamazepine 144, 183, 184, 193, 240, 278, 330, 384, 385 cardiotocography 115 case-control study 50 Catapres 399 catastrophic thinking 586, 590, 596 catastrophizing 78 catheter fibrosis, spinal 493 cauda equina syndrome 99, 211, 213 caudal approach 460 caudal block 118, 321 caudal epidural block, paediatric 321 causalgia 236, 440, 451, 452 cavernous venous sinus 185 CBT see cognitive behavioural therapy CCPAT see Chinese Cancer Pain Assessment Tool ceiling analgesic effect 144 celecoxib 101, 369, 371, 373 central pain 97, 231, 247, 370, 396, 478, 564, central sensitisation 5, 45, 96, 107, 175, 224, 230, 239,

Index 623

369, 380, 397 central sensitisation of nociception 175, 222 central summation theory of pain 11 cerebral palsy 311, 316, 322, 323, 330, 431, 557 cerebrospinal fluid leak 282, 493, 506 cervical dystonia 395 cervical spondylosis 201, 411 cervicitis 265 cervicogenic headache 157, 163, 175, 409, 411, 564 cervicothoracic ganglia 441, 453 chemical agents, for neuroblockade 148, 405, 406 chemical sympathectomy 442, 452 Chinese Cancer Pain Assessment Tool 26 Chinese pain intensity scale 26 chondroitin sulphate 260 chronic benign pain, prevalence 52 chronic pain in children, prevalence 52 chronic pain survey 50 chronic pain, after surgery 96 chronic pancreatitis 275, 290 chronic paroxysmal hemicrania 167, 172 chronic pelvic pain 275, 293 chronic sensorimotor distal symmetrical polyneuropathy 276 chronic tension type headache 173, 175, 383 chronic tophaceous gout 266 chronicity 573, 586 CIEA see continuous infusion epidural analgesia cilostazol 281 circinata balanitis 265 citalopram 278, 382 claudication, spinal, neurogenic 210 claudication, vascular 279, 301, 302, 443 clinical trials, pain research 70, 78 clinically important difference 73 clodronate 400 clonazepam 145, 394 clonidine 106, 114, 145, 147, 242, 246, 316, 322, 399, 473, 477, 492 clopidogrel 281, 304 cluster headache 158, 160, 171, 183, 370, 400, 411 cluster headache, prophylactic treatment 172 co-analgesic 99, 139, 141, 287 codeine 55, 104, 141, 165, 231, 314, 351, 352, 399, 542 coeliac plexus block 148, 292, 439, 444, 446 coeliac plexus, anatomy 444 cognitive behavioural therapy, cognitive-behavioural theory 36, 57, 119, 149, 303, 306, 329, 550, 567, 599, 612 cognitive impairment 21, 118, 285, 300, 306, 313, 385, 399, 491 Cognitive model 36 cohort study 50 colchicine 267 collaboration 613 combined spinal-epidural 117 common soft tissue rheumatism syndromes, clinical

features 269 common soft tissue rheumatism syndromes, glucocorticoid injection site & dose 269 compensation 586, 592, 608, 609 compensatory sweating 441, 450 complex regional pain syndrome 44, 231, 235, 240, 243, 248, 327, 407, 414, 427, 439, 451, 477, 503, 515, 585, 608 complex regional pain syndrome, Type I 240 complex regional pain syndrome, Type II 240 concepts of pain 9 confidence interval 66, 75, 383 confidentiality 87 constipation 103, 134, 150, 172, 277, 292, 315, 348, 351, 381, 387, 478, 491, 531, 538, 543, 544, 548, 551, 613 construct validity 24, 77, 227 content validity 77, 608 context-sensitive half-life 316 continuous infusion epidural analgesia 116 contrast agent 406, 432, 443, 461 control group 51, 71, 411, 507, 549, 568, 592 coping styles 14, 56, 601 COPM see Canadian Occupational Performance Measure core stabilisation exercise 561, 564 corneal anaesthesia 191 coronoid notch 433, 434 cortical resection 518 corticosteroid 215, 232, 288, 304, 393, 408, 412, 460, 470, 532 cortisol release 351 cost effective pain management 503 covariates 73 COX see cyclo-oxygenase COX-1 257, 304, 368, 369, 373 COX1 and COX2 inhibitors, in older persons 304 COX-2 257, 304, 368, 369, 373 cranial neuralgia 158, 181, 192 C-reactive protein 227, 262 creatine kinase 227, 288 creative hopelessness 595 criterion validity 77 critical leg ischaemia 503 Cronbach’s alphas 77 Cronbach’s coefficient alpha 77 cross excitation 238, 248 cross tolerance 142, 348, 477 cross-sectional survey 50, 208, 254 CRPS see complex regional pain syndrome CRPS, diagnostic criteria 244 cryoneurolysis of the facet joint 466 cryotherapy 242, 268, 407, 419, 462 CSE see combined spinal-epidural CT guidance (percutaneous lumbar sympatholysis) 441, 515 CT-guided lumbar sympathectomy 443 cultural factor 56, 329

624 Index

cultural relevancy 26 cultural style 55 cun 551 curved blunt needles 446, 450 cyclo-oxygenase isoenzyme-2 (COX-2) inhibitor 257 cyclooxygenase, cyclo-oxygenase 5, 99, 239, 369 cyclo-oxygenase-2 1, 5, 253, 257, 289, 323, 368 cyclosporin A 262, 266 cyproheptadine 166, 170 cytochrome P450 pathways 368 cytochrome P450-2D6 353 DALYS see disability-adjusted-life-years death rattle 543 Declaration of Helsinki 86 deconditioning 14, 38, 42, 202, 215, 256, 288, 328, 330, 601 degenerative disc disease 208, 214, 459, 468 dementia 83, 118, 300, 301, 302, 306, 545 depressed mood 38, 302, 581, 583, 590 Descartes 11 destructive pain procedures, surgical 514 dexamethasone 165, 172, 368, 398, 532, 543 dexmedetomidine 106, 323 dextroamphetamine 394 dextromethorphan 98, 107, 397 dextropropoxyphene, dextro-propoxyphene 101, 103, 141, 231, 354 diabetes mellitus 247, 268, 275, 382 diabetic amyotrophy 276 diabetic peripheral neuropathic pain 36, 275, 380 diabetic peripheral neuropathy (DPN) 52, 237, 275, 276, 382, 284, 386 diaphragmatic paralysis 446 diazepam 114, 145, 175, 323, 394, 544 diclofenac 100, 101, 144, 304, 314, 369, 372 Dictionary of Occupational Titles 575 differential sensory-motor blockade 105 digital plethysmographic techniques 443 dihydrocodeine 141 dihydroergotamine 165, 166 dihydromorphine 141 diphenhydramine 350, 400 direct vision endoscopic procedures 441 disability 600 disability-adjusted-life-years 254 discogenic pain 215, 461, 468 discography 201, 468 disease modifying anti-rheumatic drugs 257, 370 disodium pamidronate 145 disuse 601 DMARD s see disease modifying anti-rheumatic drugs dorsal column 284, 501, 514, 516, 518 dorsal horn 1, 4, 5, 7, 106, 185, 211, 223, 239, 292, 385, 399, 447, 476, 515, 549 dorsal rhizotomy 515 dorsal root entry zone destruction 515 dorsal root ganglia 1, 3, 53, 461

DOT see Dictionary of Occupational Titles dothepin 166, 170 double effect, principle of 85 DPN see diabetic peripheral neuropathy DPNP see diabetic peripheral neuropathic pain drug abuse 118, 119 drug compliance 170, 184, 339, 343 drug holiday 147 dualistic model of mankind 11 duloxetine 278, 293, 380, 382, 387 duplex ultrasound scanning 280 dysaesthesia 42, 113, 134, 149, 186, 190, 236, 436, 469, 512, 513, 517 dyspnoea 135, 137, 138, 150, 538, 542 economic burden 51, 327 ectopic nerve impulse generation 238, 248 Edmonton Symptom Assessment System 138 EECP see enhanced external counterpulsation EET see epoxyeicosatrienoic acid effect size 65, 73, 75 eicosanoids 368 electro-acupuncture 549, 564 electrotherapy, electro-therapy 215, 562 eletriptan 173 EMLA see eutectic mixture of local anaesthetics employment status 610 end of life issues 84 endorphin 27, 175, 348, 414, 549, 564 endoscopic thoracic sympathectomy 449 enhanced external counterpulsation 283 enkephalin 348 enthesopathy 265 Entonox 114, 116 environmental reinforcement 15 ephapses 238, 245 ephaptic cross talk 238 epidemiology 49 epidemiology, application of 51 epidural abscess 111 epidural analgesia 108 epidural analgesia service 116 epidural cord compression 398 epidural haematoma 111 epidural patient controlled analgesia 108, 111, 118 epidural steroid 242, 305, 398, 413, 459, 470 epidurolysis 469 epiduroscopy 469 episcleritis 261 episodic tension headache 173 epoxyeicosatrienoic acid 368 equianalgesic potency table, opioids 142 equivalence trials 72 ergonomic 35, 200, 330, 574, 576 ergot derivatives 168 ergotamine 163, 165, 166, 167, 172, 173 ESAS see Edmonton Symptom Assessment System etanercept 263, 265

Index 625

ethanol 148, 407, 419 ethical dilemma 81, 83 ethnicity 25, 49, 54, 57, 84, 95, 356, 601 etidronate 400 etodolac 369 etoricoxib 101, 369 eutectic mixture of local anaesthetics 106, 241, 326 evidence-based medicine 64, 202, 524 evoked hyperaesthetic signs 226 exercise 302, 564, 607 exercise and reactivation 607 exercise therapy 564 expectation of treatment 343 experimental design 50 extended release formulation 102 external stimulator 504 extra-articular features 261 extracorporeal shock wave therapy, extra-corporeal shock wave therapy 562, 563 extradural route 146 Faces Pain Scale 118, 313 facet joint dysfunction 210 facet joint injection 213, 412, 464 facet joints, cervical 199, 412, 462, 464 facial blushing 448 failed back surgery syndrome (FBSS), failed back syndrome 15, 210, 214, 414, 475, 502 family systems model, pain 36 fatigue 34, 38, 41, 132, 138, 161, 167, 201, 256, 385, 485, 540, 573 FBSS see failed back surgery syndrome FCE see functional capacity evaluation fear-avoidance 14, 415, 565, 581, 590, 603, 606, 607, 609 fear-avoidance beliefs 14, 568, 606, 607, 608 febuxostat 267 femoral nerve block, continuous 106, 321 femoral nerve block, continuous 106 femoral nerve block, paediatric 321 fentanyl 99, 104, 108, 117, 141, 143, 145, 311, 316, 342, 349, 352, 353, 358, 477, 479 fetal bradycardia 117 FGID see functional gastrointestinal disorders fibromyalgia 52, 194, 228, 229, 288, 340, 379, 383, 395, 408, 567, 606 Fibromyalgia Impact Questionnaire 383 fifth vital sign 313, 599 filiform needles 551 FIM see functional independence measure FIQ see Fibromyalgia Impact Questionnaire Five Element Theory 551 FLACC (faces, legs, activity, cry and consolability) 313 flunarizine 166, 169 fluoroscopy 188, 191, 406, 409, 413, 420, 469, 493, 516 fluoxetine 166, 170, 381, 382 Fontaine classification of chronic leg ischaemia 280

foramen ovale 186, 188, 189, 190, 191, 410, 434, 513 Forest Plot 66, 67 frail and disabled older person 300 frostbite 443, 449 functional assessment, pain patient’s 38, 302 functional capacity 568, 574, 608 functional capacity evaluation 608 functional gastrointestinal disorders 275, 292 functional independence measure 39 functional rehabilitation 215, 540, 599, 601, 604 functioning 39, 600 gabapentin 114, 144, 166, 184, 215, 240, 248, 278, 305, 330, 384, 479 gait 43, 210, 226, 256, 324, 385, 431, 478, 568, 602, 606 gamma-aminobutyric acid inhibitory system 144 gamma-aminobutyric acid, neurotransmission 144, 384 ganglion impar, ganglion of impar 148, 444, 446, 448 ganglionectomy 443, 515 Gasserian ganglion 185, 186, 433, 511 gastrointestinal complications associated with NSAID use 257 gastrointestinal pain syndromes, in HIV/AIDS 286 gastro-oesophageal reflux disease 284 Gate Control Theory, gate-control theory 12, 13, 414, 501, 518 gender 19, 49, 53, 82, 254, 284, 352, 601 genetic polymorphism 55, 141, 353 GERD see gastro-oesophageal reflux disease glossopharyngeal nerve 192 glossopharyngeal neuralgia 192 glucocorticoids 255, 262, 268 glucosamine, glucosamine sulphate 260 glucose-6-phosphate dehydrogenase deficiency 331 glycated haemoglobin 277 glycerol gangliolysis 186, 191 goal setting 14, 303, 329, 561, 568, 577, 581, 600, 605, 613, 615 gold salts 262 gout, prevalence 266 gout, epidemiology 266 gouty arthritis 266 graded exercise 567 Gray (Gy) 348 greater occipital nerve block 175, 331, 411 greater occipital nerve block, for headache 170, 175 greater splanchnic nerve 444, 445 greater trochanter 265, 435, 556 guanethidine 246, 412, 440 guidelines for OA management 259 gustatory sweating 443, 450 HAART see highly active anti-retroviral therapy haemophilia 288 half-body irradiation 529, 530 Hartel’s technique 513 HbA1c see glycated haemoglobin

626 Index

headache 157 Heberden’s nodes 258 heparin 111, 281, 542 heterogeneity 64, 65, 66, 222, 348, 502 highly active anti-retroviral therapy 285 HIS see International Headache Society histamine 4, 45, 238, 304, 323, 350, 381, 393, 400, 491, 527, 543 historical perspectives, of pain 10 HLA B27 see human leucocyte antigen B27 HLA-B*1502 allele 184 holistic approach 136, 150, 568 Horner’s syndrome 161, 423, 441, 450, 451, 515 Huber needle, atraumatic 146 human immunodeficiency virus (HIV) 85, 255, 275, 277, 285 human leucocyte antigen B27 264 hyaluronan derivatives 260 hydromorphone 102, 104, 108, 118, 142, 314, 349, 477, 484, 494 hydrophilic opioid 103, 110, 481, hydrotherapy 265, 561, 564 hydroxychloroquine 262 hydroxyzine 400 hyperaesthesia 44, 45, 192, 236 hyperalgesia 3, 6, 42, 73, 103, 223, 227, 236, 237, 302, 348, 380, 399, 492 hypercalcaemia 400, 543 hyperechoic 423 hyperhidrosis 439, 441, 448, 451, 453, 515 hyperpathia 236, 237, 240, 247 hyperuricaemia 266, 267 hypnosis 114, 115, hypocalcaemia 400 hypoechoic 423 hypophysectomy 518 hypothalamotomy 518 hypoxaemia 94, 108, 115, 171, 172 IASP see International Association for the Study of Pain ibandronate 400 IBS see irritable bowel syndrome ibuprofen 99, 100, 144, 165, 232, 313, 317, 369, 372, 543 ICF see International Classification of Functioning, Disability and Health ICF Core Set 601, 602 ICHD-II see International Classification of Headache Disorders, second edition IDET see intradiscal electrothermal procedure, intradiscal electrothermal annuloplasty IL-1 see interleukin-1 IL-6 see interleukin-6 ilioinguinal nerve block, paediatric 318, 319 illness behaviour 15, 43, 564, 565, 592, 609 Iloprost 281 image intensifier guided blocks 443 imagery training 577

implantable spinal drug delivery system 413 implantable stimulator 501 implanted pulse generator 505 implanted receiver 505 incident pain 133, 137, 147, 340, 341, 474 indomethacin 100, 101, 144, 165, 166, 172, 267, 314, 369 inflammatory bowel disease 255, 264, 265 inflexible and perfectionistic attitude 585 infliximab 263, 265 informed consent 82, 86, 87, 420 insomnia 132, 135, 138, 144, 150, 339, 382, 394, 460, 538, 541 institutional guidelines, opioid therapy 119 institutional review board 89 instrumental delivery, analgesia for 117 insurance 611 integrated palliative care service 540 intercostal nerve block 148, 409, 427, 428 intercostal nerve, anatomy 427, 428 intercostobrachial nerve 134, 426 interdisciplinary approach 327, 541, 567 interferential current stimulation 562 interferential therapy 561, 562 interlaminar approach 414, 460 interleukin-1 6, 239, 263, 323, 368 interleukin-6 6, 263 intermittent “top-up” 116 intermittent claudication 279, 280, 281 internal consistency 26, 77 International Association for the Study of Pain 13 International Classification of Functioning, Disability and Health 39, 600 International Classification of Headache Disorders, second edition 158, 162 International Headache Society 158, 193 interscalene groove 420, 425 intervertebral disc degeneration 56 intra-articular injection 99, 106, 464, 465 intraclass correlation coefficient 77 intractable angina pectoris, SCS 503 intradiscal electrothermal procedure, intradiscal electrothermal annuloplasty (IDET) 201, 215, 469 intramuscular 99, 113, 116, 117, 141, 168, 225, 267, 312, 342, 351, 373, intranasal 99, 104, 108, 143, 168, 172, 243, 246 intranasal PCA 108 intrathecal 99, 104, 107, 117, 146, 214, 239, 243, 316, 322, 350, 413, 460, 473, 512 intrathecal drug delivery 414, 473, 512, 519 intrathecal granuloma 494 intrathecal morphine 97, 104, 110, 117, 146, 487 intrathecal opioid 110, 117, 146, 214, 350, 413, 476, 490 intrathecal route 132, 146, 399, 476 intravenous 46, 99, 102, 107, 110, 139, 143, 168, 185, 231, 243, 246, 311, 316, 326, 331, 342, 349, 351, 373, 440, 468, 490, 545

Index 627

intravenous morphine infusion regimen 143 intravenous paracetamol 100, 313, 315 intravenous regional sympathetic block 412 iontophoresis 99, 104, 108, 143, 326 IPG see implanted pulse generator ipsilateral coeliac ganglion 445 iritis 264 irritable bowel syndrome 53, 292, 293 ischaemic rest pain 280, 443, 503 ischial tuberosity 434, 435, 436 JCAHO see Joint Commission on Accreditation of Healthcare Organizations Joint Commission on Accreditation of Healthcare Organizations 313 justice 82, 89 Kenner’s classification, acupuncture 549 keratitis 190, 191 keratoconjunctivitis sicca 261 keratoderma blenorrhagicum 265 ketamine 98, 107, 114, 115, 141, 145, 147, 243, 281, 313, 315, 323, 396, 397, 479 ketamine isomer 396, 397 ketamine, intrathecal 479 ketamine, racemate 396 ketoprofen 100, 101, 144, 232 ketorolac 100, 101, 166, 314, 317, 371, 479 kinins 4, 5 kyphoplasty 214, 459, 470 L’Abbé Plot 66 labour pain 115 labour pain, anatomy of 115 lamotrigine 185, 247, 278, 287, 384, 385 language, older person’s 300, 306 LBP see low back pain lead breakage 505, 506 lead configurations 502 lead migration 505, 506 leflunomide 262, 265 Lequesne indices 555 lesser splanchnic nerve 445 leukotrienes 1, 4, 368, 373, 378, levo-bupivacaine 105 licofelone 373 life direction 594 life roles 34, 38, 39, 40, 573, 576, 578 life trajectory, cancer patient 537, 538, 540 lignocaine 46, 105, 109, 114, 145, 168, 172, 241, 246, 278, 326, 398, 407, 412, 466, 469 lignocaine intra-nasal 4% 172 limb dystonia 395 lionine facial appearance 171 lipophilic opioid 103, 104, 110 liposome encapsulated extended release morphine 110 lipoxygenase 368, 369, 372, 373, 378 lithium 172

litigation 592, 609 LLUMC Activity Sort 575 LMWH see low molecular weight heparin local anaesthetic blockade 440 local anaesthetic class 1B antiarrhythmic agent 398 local anaesthetic toxicity 105, 423 local anaesthetics 105, 106, 144, 146, 173, 192, 215, 241, 243, 258263, 269, 317, 318, 407, 461, 468, 478, local infiltration 98, 106, 149, 326, 411 local-field radiotherapy 527, 530 loperamide 348 lorazepam 114, 145, 394, 544 loss of corneal reflex 190 loss of functional abilities 583 loss of proprioception 117 low back pain 13, 39, 42, 50, 55, 199, 200, 207, 208, 210, 211, 213, 237, 253, 264, 279, 370, 383, 413, 459, 471, 484, 547, 555, 589, 601, 608 low back pain, inflammatory 264 low molecular weight heparin 111, 281 lower limb ischemia 443 lumbar facet joint 412, 413, 462 lumbar ganglia 441, 453 lumbar sympathectomy 282, 439, 443, 515 lumbar sympathetic chain 441, 442, 450 lumbar sympatholysis 442, 443 lumiracoxib 100 MAC see monitored anaesthetic care mandibular nerve block 433 mandibular nerve, anatomy 434 mandibular nerve, mandibular branch see trigeminal nerve, mandibular branch manual therapy 203, 268, 561, 563 MAOI see monoamine oxidase inhibitor masked depression 12 masseter muscle 190, 193, 513 MASTER trial 112 maternal fever 117 maxillary nerve block 433 maxillary nerve, anatomy 433 maxillary nerve, maxillary branch see trigeminal nerve, maxillary branch McGill Pain Questionnaire 19, 23, 73, 137, 555 McKenzie exercises 564 MEAC see minimal effective analgesic concentration Meckel’s cave 185, 186, 191 medial branch block, facet joint 462, 464 medial thalamotomy 517 median nerve 421, 422, 427 medical ethics 81, 82, 89 Medical Outcomes Study 36-Item Short-Form Health Survey 39, 52 meditation 56, 596 melatonin 173 meloxicam 101, 323, 369 Melzack and Wall 12, 414, 501

628 Index

Memorial Pain Assessment Card 138 meperidine see pethidine mesencephalotomy 517 meta-analysis 64, 65 metastatic bone disease 398, 400 metastatic plexopathy 533, 534 methadone 101, 104, 119, 141, 278, 287, 348, 354, 357, 477, 542 methaemoglobinaemia 106 methotrexate 262, 265 methylphenidate 140, 173, 393 methysergide 166, 170 metoprolol 166, 169 metrizamide 139, 186 mexiletine 242, 247, 398 micro-acupuncture 557 microvascular decompression 182, 191, 305, 511, 512, 519 midazolam 107, 114, 145, 321, 322, 326, 394, 479, 488, 545 midazolam (intrathecal) 479 midline myelotomy 517 migraine 53, 548, 553, 160, 162, 287, 300, 342, 381, 384, 398, 548, 553 migraine with aura 160, 162, 164 migraine without aura 162, 164 migraine, beta-blockers 166, 169 migraine, pathogenesis 163 migraine, prophylactic therapy 169 minimal effective analgesic concentration 140 mixed agonist-antagonists 119 molecular mimicry 264 monitored anaesthetic care 188, 420 monoamine oxidase inhibitor 97, 102, 166, 168, 170, 353, 379 monoamine oxidase inhibitors, interaction with pethidine 353 monosodium urate crystals 266 morpheus 347 morphine 55, 97, 142, 146, 215, 231, 281, 289, 314, 342, 347, 351, 387, 394, 476, 487, 542, morphine 3-glucoronide 316 morphine bioequivalent conversion (ratio) 476 morphine syrup 142, 146 morphine, preservative free 142, 147 morphine, rectal 142 morphine, slow release preparations 141, 142 morphine-6-glucuronide 352 motor cortex stimulation 519 moxibustion 551, 555 MPAC see Memorial Pain Assessment Card MPI see Multidimensional Pain Inventory MPQ see McGill Pain Questionnaire MPS see myofascial pain syndrome multi-contact electrodes 505 multidimensional assessment, pain 32, 43 Multidimensional Pain Inventory 39, 74 multidimensional scales, multi-dimensional scales 19,

20, 25, 137 multidimensional tools, older person 301 multidimensionality 20, 540 multidisciplinary approach to NSLBP 215 multidisciplinary pain rehabilitation programs 611 multimodal analgesia 141, 288, 313, 343 multiple lead systems 502, 505 multiple sclerosis 238, 247, 475, 512, 182, 185, 192 mu-opioid receptor 102, 380 Muscle biopsy 228 muscle nociception 222, 225, 226 muscle strength evaluation 605 musculocutaneous nerve 421, 422, 423, 427 musculoskeletal and rheumatoid Pain 370 myalgia 172, 194 myofascial pain 194, 221, 221, 228, 381, 395, 398, 408, 467 myofascial pain dysfunction syndrome 193 N-acetyl-p-benzo-quinone imine 374 nadolol 166, 169 naloxone 103, 116, 247, 348, 350, 355, 359, 414, 491 naproxen 100, 101, 116, 144, 165, 169, 314, 370 nasal preparation 143, 167 neck pain, definition 199 negatively birefringent urate crystals 266 neostigmine 107, 147, 321, 479 nerve block, older persons 305 nerve block, paediatric 313, 318 nerve growth factor 3, 4, 133, 287 nerve stimulator 106, 318, 321, 331, 406, 432, 435, 466, 552 neural blockade 46, 405, 406, 419 neuraxial analgesia, cancer pain 146 neuraxial analgesia, definition 473 neuroablation of the trigeminal nerve 173 neuroablative block, limitations of 149 neuroablative procedures 132, 148, 193, 415 neuro-augmentation for pain management 518 neuroblockade, physical means 407 neurodevelopmental aspects, foetus 311 neurodynamics 563 neurogenic claudication 210 neurogenic inflammation 163, 167, 172, 395, 407, 563 neurokinin 1 4 neurolysis 148, 242, 293, 324, 421, 446, 447, 448, 450, 452, 515 neurolytic agents 407, 440, 450 neurolytic coeliac plexus block 148, 291, 446 neurolytic keratitis 190 neurolytic sympathetic blockade 443 neuroma 134, 182, 238, 242, 467, 514 neuronal hyperexcitability 2, 163 neuropathic pain 3, 36, 52, 96, 106, 141, 184, 208, 230, 235, 275, 324, 340, 354, 370, 379, 394, 412, 439, 451, 474, 483, 502, 511 neuropathic pain, epidemiology 237 neuropathic pain, IASP classification 240

Index 629

neuropathic pain, pathophysiology 238 neuropathic pain, prevalence 52, 237 neuropathy, acute Charcot 277 neuropathy, asymmetric proximal diabetic 276 neurostimulation 148, 293, 502 neuroticism 15, 582, 592, 609 neurotoxicity 107, 133, 173, 286, 477 neurotoxicity, spinal analgesics 477 NGF nerve growth factor nitric oxide synthase 5, 349 NK1 see neurokinin 1 NMDA 1, 5, 98, 107, 239, 243, 349, 354, 380, 396, 477, 492 NMDA antagonist 107, 142, 143, 145, 380, 397, 479, 492 NMDA glutamate receptor 396, 397 NMDA receptor 1, 5, 98, 107, 239, 243, 349, 354, 380, 396, 477, 492 N-methyl D-aspartic acid receptors antagonists see NMDA antagonist N-methyl-D-aspartate see NMDA N-methyl-D-aspartate receptors see NMDA receptor N-methylnaltrexone 348, 351 NNH see number needed to harm NNT see number needed to treat nociception 3, 6, 7, 14, 15, 34, 54, 175, 221, 222, 226, 517 nociceptive pain 36, 40, 44, 95, 114, 222, 235, 237, 247, 286, 340, 475, 483, 490, 514, 519 nociceptor sensitisation 238 nociceptor: thermal, mechanical or chemical 3, 4 nociceptors 3, 4, 7, 12, 42, 93, 132, 175, 208, 211, 222, 224, 238, 240, 279, 323, 395, 407, 447 nodal OA 258 nomenclature, problem with muscular pain conditions 222 nonadrenergic imidazoline receptors 399 non-communicative patient 118 non-inferiority 72 nonmaleficence 82 non-pharmacological management, in older persons 302 non-specific esterases, remifentanil metabolism 355 non-specific low back pain 50, 207, 210, 214, 215, 462, 555 non-steroidal anti-inflammatory drugs 93, 98, 99, 132, 139, 144, 163, 165, 170, 175, 215, 216, 232, 232, 240, 257, 267, 304, 313, 317, 323, 331, 344, 348, 367 norpethidine 101, 113, 116, 290, 353 nortriptyline 145, 166, 170, 247, 305, 381, 387 NRS see numerical rating scale NSAIDs see non-steroidal anti-inflammatory drugs NSLBP see non-specific low back pain number needed to harm 69 number needed to treat 66, 68 numerical rating scale 21, 42, 73, 74, 78, 118, 137, 301, 313 Nuremberg Code 81, 86

nutriceuticals

260

O*NET 575 observational charts, older person 301 observational study 50 obturator foramen 431 obturator nerve block 431 occipital nerve injection 172, 173 occupational therapist, role in rheumatoid diseases 256 occupational therapy 573 odds, odds ratio 51, 66, 67, 68 ODI see Oswestry Disability Index OIH see opioid induced hyperalgesia older persons, pain in 299 older persons, prevalence 52, 299 Operant Behavioural model, pain 36 opioid 6, 53, 55, 83, 100, 139, 141, 165, 214, 231, 240, 259, 278, 304, 315, 340, 347, 380, 473, 484, 542, 543, 549 opioid abuse 357 opioid addiction 141, 305 opioid administration 85, 104, 142, 143, 146, 349, 351, 490 opioid analgesics 347 opioid contract 358 opioid dependence 103, 289, 305, 347, 357, 358 opioid depressed suckling behaviour 358 opioid induced hyperalgesia, opioid-induced hyperalgesia 103, 193, 119, 348, 492 opioid prescription diversion 305, 357, 542 opioid receptors 6, 102, 140, 146, 311, 347, 380, 396, 473, 476, 491 opioid sparing effect 370 opioid tolerance 103, 348, 477 opioid use, lactation 358, 359 opioid withdrawal 119, 145, 323, 354, 355 opioid, in older persons 304 opiophobia 356 oral intake 97, 99, 134, 185 oral mucositis 134 oral transmucosal 104, 114, 143, 353 oral transmucosal fentanyl citrate 104, 114, 143, 353 organisational ethics and public health ethics 89 orphenadrine 400 osteoarthritis, incidence of 258 osteoarthritis, economic consequences 258 osteoarthritis, osteo-arthritis 52, 87, 258, 280, 300, 370, 400, 555, 601 osteoarthritis, prevalence 258 osteoclast 133, 145, 400, 527 osteoclast, osteoclastic activities 133, 145, 400, 527 osteonecrosis 256, 288 osteophytosis 259 osteoporosis and metastatic bone disease, bisphonates for 400 osteoporotic vertebral fracture 210 Oswestry Disability Index 575 Oswestry Low-Back Pain Disability Questionnaire 39

630 Index

OTFC see oral transmucosal fentanyl citrate outcome domain 74 outcome goals 613 outcome measure, outcome measurement 39, 50, 63, 73, 87, 88, 383, 502, 554 outcome, epidural analgesia 112 oxcarbazepine 384, 385 oxycodone 102, 104, 108, 142, 231, 278, 314, 316, 349 oxymorphone 102 p.r.n., PRN see pro-re-nata P-32 see phosphorus-32 pacing skill 38, 568 PAD see peripheral arterial disease paddle electrodes 502, 505 PAG see periaqueductal gray (PAG) Paget’s disease 245, 256, 400 pain and memory 6 pain as a response 16 pain assessment 15, 19, 32, 34, 45, 55, 63, 78, 107, 118, 138, 226, 301, 313, 356, 397 pain associated consequences 37 pain behaviour, examination of 43 pain behaviours 14, 15, 19, 43, 55, 97, 210, 213, 312, 325, 356, 415, 606, 609, 611 pain contributors 31, 34, 35, 36, 37, 41 pain disorder 11, 202, 588 pain experience 10, 15, 19, 32, 38, 43, 51, 73, 93, 222, 236, 575, 590, 596, 610 pain in older person, epidemiology 299 pain mechanism at molecular level 132 pain modulating modalities 562 pain modulation 7, 53, 293, 561, 562, 565, 568 pain reporting 12, 19, 32, 44, 49 pain research, ethics 86 pain sensitivity 6, 53, 190, 287, 300, 341, 349 pain tolerance level 236 pain, clinical assessment of 222 pain, definition 9, 13, 16, 31 pain, definition by IASP 31 Painad 301 painful peripheral neuropathy 287, 300 pain-prone personality 15, 95 palliative care, WHO definition 537 palmar sweating 448, 450 pamidronate 145, 246, 400 pancreatic cancer pain 445 paracervical block 118 paracetamol 93, 99, 100, 144, 167, 175, 215, 231, 293, 303, 313, 354, 367, 373 paracetamol injection 100 paracetamol toxicity 374 paraesthesia 40, 42, 106, 134, 168, 176, 189, 237, 247, 269, 283, 386, 406, 414, 422, 430, 466, 492, 494, 504, 506 paraspinal muscle spasm 395 paravertebral block 442 parecoxib 100, 314, 317

paroxetine 278, 381, 382 pathophysiology of pain, in osseous metastases 526 patient autonomy 83, 85, 542 patient controlled epidural analgesia 116 patient evaluation 33, 93, 96, 137, 339, 604 Patient Global Impressions of Improvement score 383 patient-controlled analgesia 55, 107, 139, 143, 289, 315 patient-controlled incisional regional analgesia 108 patient-controlled intranasal analgesia 143 patient-controlled transdermal system 105, 108 pattern theory, of pain 12 PBCR see percutaneous balloon compression rhizotomy PCA see patient-controlled analgesia PCEA see epidural patient controlled analgesia PCEA see patient controlled epidural analgesia PCINA see patient-controlled intranasal analgesia penicillamine 262 penile block 319, 322 percutaneous anterolateral cordotomy 148 percutaneous balloon compression rhizotomy 191 percutaneous electrodes 505 percutaneous lumbar sympatholysis 442 percutaneous radiofrequency rhizotomy 186, 188, 190, 191, 511, 513 percutaneous splanchnic block 444 periaqueductal gray (PAG) 348 peri-articular rheumatic diseases 267 peri-articular and regional rheumatic pain syndromes 267 perineural injection 99, 105 peripheral arterial disease 279 peripheral nerve injury 398 peripheral neural analgesia 106, 119 peripheral neurectomy 511, 514 peripheral vascular disease 168, 275, 301, 302, 305, 414, 439, 442, 453, 502 periventricular grey 519 persistent non-cancer pain, in older persons 301 persistent pain 3, 31, 34, 38, 44, 55, 82, 88, 115, 214, 221, 293, 299, 303, 327, 330, 399, 479, 495, 585 persistent pain, paediatric 327 personality disorders 475, 591, 592 pethidine 101, 104, 108, 112, 116, 140, 165, 167, 290, 353, 479 pethidine, anti-shivering effects 353 pethidine, epidural 117 PGI-I see Patient Global Impressions of Improvement score phantom pain 134, 242 pharmacogenetic 55 pharmacological management, in older persons 302 pharmacological modification of sensitisation 230 phenelzine 166, 169, 170 phenol 148, 242, 282, 324, 407, 410, 419, 430, 434, 442, 450, 467 phenol 10% 442, 443 phenomenon of spread and self devaluation 585 phentolamine 46, 246, 515

Index 631

phenytoin 185, 278, 384, 386 PHN see post herpetic neuralgia phospholipase A2 368, 378, 460 phosphorus-32 525, 530 physical activity 38, 160, 162, 174, 256, 303, 577, 603, 607 physical and psychosocial burden 581 Physical Functional Capacity evaluation 39 physiological dependence 102 physiotherapists, role in rheumatoid management 256 physiotherapy, psychological factors 565 PID see prolapsed intervertebral disc piroxicam 100, 101, 232 pizotyline 170 placebo 64, 67, 71, 83, 87, 110, 168, 228, 230, 283, 304, 344, 371, 382, 397, 439, 464, 476, 515, 549, 555, 562 placebo analgesia 83 placebo control 64, 71 placebo effect 71, 87, 230, 231283, 304, 339, 344, 412, 452, 562 placebo surgery 87 plantar fasciitis 270, 408, 409, 563 pluripotent cells 557 PMPS see post-mastectomy pain syndrome pneumothorax 112, 409, 423, 429, 430, 446, 450, 542, 557, 558 polyanalgesic approach, spinal 480 polymorphism, isoenzyme cytochrome P450 2D6 141 polymorphisms in genes coding 53 positive coping with pain 577 positive versus negative affect 591 postdural puncture headache 111, 117, 493 postherpetic neuralgia 52, 134, 172, 181, 183, 184, 192, 241, 286, 301, 304, 305, 379, 384, 396, 397, 411, 448, post-mastectomy pain syndrome 134 postoperative pain management, older persons 305 post-thoracotomy pain syndrome 134 potassium channel 4, 384, 478 preeclampsia 100 pre-emptive analgesia 97, 98 pregabalin 6, 145, 192, 241, 278, 305, 330, 384, 386, 387 preganglionic fibres 411, 441 pre-terminal patient 144 preventive analgesia 97 prevertebral fascia 420 PRFR see percutaneous radiofrequency rhizotomy primary headache 158 primary hyperalgesia 222 problem solving approach 204 procedural pain, burn 114 procedural pain, paediatric 325 procedure specific postoperative pain productivity 34, 40, 51, 254, 573 progressive gangrene and ulceration 443 prolactin 351

prolapsed intervertebral disc 208 prolonged labour 117 propacetamol 100, 315 propanolol 169, 173 prophylactic antibiotic 289, 470, 505 propoxyphene 102, 259, 354 propoxyphene cardiotoxicity 354 pro-re-nata 140, 314, 340 prospect group 95 prostaglandins 1, 4, 6, 133, 170, 224, 238, 257, 281, 323, 368, 372, 527 prostanoids 4, 6, 323, 368, 373 proteoglycan synthesis 260 provocative test, neck pain 201 pruritus 4, 98, 110, 116, 138, 460, 491 pseudo-addiction, opioid 357 pseudo-addiction, pseudoaddiction 119, 340, 357 psoriasis 264, 265, 400 psychiatric disorder 158, 285, 339, 503, 589 psychoanalytic model, pain 36, 37 psychogenic pain disorder 11 psychological consequences 38, 328, 586 psychological dependence 103, 215, psychological factor 11, 12, 37, 51, 56, 113, 204, 211, 245, 293, 415, 474, 565 psychological intervention 138, 418, 550, 593 psychological meaning of injury site 584 psychological modulation of pain 14 psychological pain contributors 36 psychological technique 114, 115, 149 psychomimetic effect 107, 354 psychophysical measures, older person 300 psychophysical studies 229 psychoprophylaxis 115 psychosocial factors 38, 40, 53, 63, 199, 212, 293, 327, 589, 596 psychostimulants 394 PTCS see patient-controlled transdermal system PTPS see post-thoracotomy pain syndrome pudendal nerve block 118 pulmonary embolism 117 pulsed radiofrequency 408 pulvinarotomy 518 punctate hyperalgesia 5, 6, 42 purinergic receptors 4 p-value 75 PVG see periventricular gray Qi 550, 551, 552 quadripolar leads 505, 506 quantitative sensory testing 45 question mark posture 264 radial nerve 421, 422, 427 radicular pain 15, 199, 240, 386, 414, 494, 502, 503, 531 radiobiology, principles of 526 radiofrequency cannulae 446

632 Index

radiofrequency coagulation 419 radiofrequency generator 187 radiofrequency lesioning, facet joint 465 radiofrequency medial branch neurotomy 412, 415 radiofrequency treatment 407 radiofrequency, conventional 408 radiosurgery 173, 185, 198, 411, 511, 514 randomisation 70, 76 rasburicase 267 rater reliability 26, 77, 609 Raynaud’s disease 245, 440, 441, 443 Re-186 see rhenium-186 reactive arthritis 264, 265, 287 rechargeable system 505 re-conceptualisation 614 red flags, symptoms 200, 202, 211, 213 reducing control 595 referred pain 199, 208, 211, 222, 225, 226, 229, 292, 304, 408, 411, 459, 461 reflex sympathetic dystrophy 243, 414, 429, 452 re-formulation 614 Reiter’s syndrome 255, 264, 265, 287 relapse, into disability 615 relative risk 67, 286, 372 relative risk reduction 67, 286, 372 relaxation 38, 114, 149, 163, 175, 194, 265, 303, 323, 329, 408, 421, 491, 550, 558, 561, 564, 566, 577, 578, 593, 596, 615 release of nociceptor input 239, 248 reliability 19, 21, 24, 25, 26, 39, 77, 227, 229, 313, 324, 505, 604, 609, 616 remifentanil 101, 108, 114, 314, 316, 352, 355 René Leriche 440, 451 respiratory depression 85, 97, 98, 103, 108, 111, 114, 142, 305, 315, 341, 344, 348, 350, 353, 354, 358, 477, 479, 491, 495, 519 responsiveness 1, 4, 78, 169, 224, 245, 265 resuscitation 112, 113, 116, 323, 359, 496 retroperitoneoscopic surgical sympathectomy 443 return-to-work 574, 576, 610, 611 Reye’s syndrome 317 RF see rheumatoid factor rhenium-186 531 rheumatoid arthritis 56, 194, 225, 253, 260, 327, 370, 400, 429, 601 rheumatoid arthritis, biologic agents for 263, 268 rheumatoid arthritis, clinical manifestation 261 rheumatoid arthritis, epidemiology 253 rheumatoid factor 260, 262 rheumatoid nodules 260 rheumatological pain syndrome, in HIV/AIDS 287 risk 66 risk factors, incidence and progression of osteoarthritis 258 rituximab 263 rofecoxib 100, 304, 317, 369, 373 rofecoxib, cardiac effect 371 Roland and Morris Disability Survey 39

role of personality 15, 16 Rome III Classification System of FCID 292 root sleeve injection 461 ropivacaine 105, 106, 108, 110, 112, 116, 118, 281, 314, 317, 321, 322, 407, 478, 479 RSD see reflex sympathetic dystrophy sacrococcygeal disc 448 sacroiliac joint pain 215, 467 sacro-iliitis 265 salicylate 147, 266, 367, 368 samarium-153 (Sm-153) 531 sample size 72 SARS see severe acute respiratory syndrome Satisfaction with Performance Scaled Questionnaire 575 scalene muscles 420, 422, 425 scalp acupuncture 557 sciatic nerve block 106, 419, 434 sciatic nerve, anatomy 434 sciatica 208, 211, 213, 264, 280, 413, 461, 548 SCIM see Spinal Cord Independence Measure scleritis 261 SCS see spinal cord stimulation secondary handicaps 585, 590 secondary headache 158 secondary hyperalgesia 5, 222, 224, 226, 228, 229, 230, 239, 323, 369, 397 selective COX-2 inhibitors 100, 257, 304, 323, 372, 373 selective enrolment 76 selective serotonin reuptake inhibitor 166, 170, 305, 379, 545 self-care 138, 278, 573, 600 self-efficacy beliefs 14 self-esteem 327, 328, 541, 573, 583, 591 self-instruction 577 self-management 37, 57, 256, 612, 615 semi-synthetic opioid 102 sensory dysaesthesia 134, 186 sensory theory of pain 10 seroma 493 seronegative arthritis 264 seronegative SpA 264 serotonin norepinephrine reuptake inhibitor 278, 379, 381, 382, 386, 387 serotonin syndrome 102, 353, 354 serotonin, role in descending inhibition 380 severe acute respiratory syndrome 288 sex, gender 53 SF-36 see Medical Outcomes Study 36-Item Short-Form Health Survey sham acupoints 549 shock 112 sickle cell disease 289, 331 Sickness Impact Profile 39 Silas Weir Mitchell 451 silent nociceptor 3, 4 SIP see Sickness Impact Profile

Index 633

SIP see sympathetically independent pain skeletal muscle tone 441 sleeping, nociceptor 3 SMP see sympathetically maintained pain snowballing impact, of chronic pain 583 SNRI see serotonin norepinephrine reuptake inhibitor social compensation 37, 38 social discrimination and racism 56 social factor 56 social Modelling theory 36 social pain contributors 37 social phobia 441 social phobic reactions 441 sodium valproate 166, 169, 243, 330, 384 soft tissue rheumatism 228, 256, 267, 269 somatic pain 340, 448 somatic referred pain 225 spasmodic torticollis 395 spastic paralysis 441 specific low back pain 208 specificity theory of pain 11 sphenopalatine ganglion block 173 spinal cord compression 98, 111, 136, 492, 494, 531, 532 spinal cord compression, radiotherapy for 531 Spinal Cord Independence Measure 39 spinal cord stimulation 214, 242, 247, 278, 282, 283, 293, 399, 414, 470, 475, 501, 512, 518 spinal cord stimulation, current-controlled 505 spinal cord stimulation, in peripheral arterial diseases 282 spinal cord stimulation, in refractory angina 283 spinal cord stimulation, systematic review 502, 503 spinal cord stimulator electrode 501, 502, 504, 505, 506 spinal cord stimulator, battery life 483, 502, 505 spinal cord stimulator, cost benefit analysis 506 spinal cord stimulator, haematoma 492, 505, 506 spinal cord stimulator, infection 505, 506 spinal cord stimulator, programming 505, 506 spinal cord stimulator, quality of life improvement 503 spinal cord stimulator, voltage-controlled 505 spinal stenosis 207, 210, 214, 280, 460, 469, spiritual contributors, pain 37 splanchnic and coeliac plexus blockade 439 splanchnic blockade, splanchnic nerve neurolysis 446 splanchnic nerves 291, 439, 441, 444, 445, 446 splanchnic nerves, anatomy 444 splanchnic-coeliac plexus 441, 453 spondyloarthritis 255, 264 spondyloarthritis, clinical manifestation 264 spondylolisthesis 208, 209, 211, 214, 460, 469 spondylosis 201, 210, 411, 460 spontaneous pain 36, 224, 237, 239, 240, 302, 554 SPSQ see Satisfaction with Performance Scaled Questionnaire Sr-89 see strontium-89 SSRI see selective serotonin reuptake inhibitor stellate ganglion 243, 246, 440, 449, 450

stellate ganglion, anatomy 449 stereotyping 55, 57 stocking and glove distribution, in diabetes mellitus patients 276 strabismus 395 strontium-89 531 study design 49, 67, 73, 87, 260, 412 stump pain 134, 240, 242, 243, 248, 301 subchondral sclerosis 259 subclavian artery 420, 425 subcostal nerve 427, 428 subcutaneous 99, 100, 102, 108, 139, 143, 145, 166, 172, 243, 246, 260,266, 280, 318, 321, 326, 342, 349, 414, 428, , 481, 490, 493, 543 subcutaneous nodules 260, 261 subjectivity and multidimensionality of symptoms 540 sublingual 99, 104, 116, 143, 168, substance P 1, 3, 4, 5, 133, 163, 268, 385, 399, 400, 407, 414, 477, 478, 527 substance use disorder 94, 357 sudomotor blockade 443 sufentanil 99, 101, 104, 110, 112, 116, 118, 477, 479 sulindac 144 sulphasalazine 262, 265 sumatriptan 165, 166, 167, 172, 370 summary measure of effect 66, 75 superficial heat 303, 567 superior hypogastric plexus 148, 441, 447, 453 superior hypogastric plexus, anatomy 441 supraorbital nerves 170 suprascapular nerve block 409, 411, 429, suprascapular nerve, anatomy suprascapular notch 429 surgical sympathectomy 282, 440, 443, 451, 452 switching of analgesics 132, 143, 145, 168, 342, 344, 349 sympathetic afferents 441, 447 sympathetic block, sympathetic blockade 42, 110, 113, 242, 243, 245, 246, 330, 405, 411, 412, 439, 515 sympathetic chain 439 sympathetic chain, cervical 449 sympathetic ganglia 441, 444 sympathetic nervous system 283, 411, 441, 445, 447, 448, 449, 451, 452 sympathetically independent pain 243, 452 sympathetically maintained pain 238, 243, 245, 412, 451, 515 syndesmophytes, bony deposition 265 syndrome X 284 synthetic opioid 101, 102, 353, 354 synthetic phenylpiperidine 353 systematic review 64 systemic local anaesthetic type drugs 398 TAO see thromboangiitis obliterans TCA see tricyclic antidepressant TCM see Traditional Chinese Medicine Tegretol 144, 184

634 Index

temporo-mandibular joint, temporomandibular joint 161, 193, 194 tenderness 43, 158, 174, 194, 201, 203, 212, 222, 223, 224, 226, 260, 269, 270, 462, 467 tenderness, muscle 222, 223, 224, 226 tennis elbow 222, 269, 408, 409, 548 TENS see Transcutaneous Electrical Nerve Stimulation tension headache, tension-type headache 157, 158, 161, 170, 173, 174, 175, 370, 383, 395, 409, 411, 553 tension-type headache, prevalence 173 tension-type headache, preventive treatment by TCA & duloxetine 383 teratogenic drugs 342 test-retest reliability 77, 609 TEW needle 187, 188 thalidomide 265 therapeutic transdermal system 353 thermal rollers 45 thermocouple electrode 187, 188 thermography 45 thoracic outlet syndrome 395 thoracoscope 441 thoracoscopic sympathectomy 441, 443 threshold and tolerance, older person 300 thromboangiitis obliterans 245, 279, 280 tic douloureux 181, 394, 395 tiludronate 400 TMJ see temporo-mandibular joint TMR see transmyocardial revascularization TNF-alpha see tumour necrosis factor-alpha TNF-alpha antagonists 263, 265 tolerance, opioid 103, 105, 107, 140, 147, 163, 277, 343, 348, 349, 351, 354, 356, 357, 358, 397, 474, 477, 480, 491, 496, topiramate 166, 170, 278, 384, 385, 386, 387 total spinal anaesthesia 423 toxicity, paracetamol overdose 374 Traditional Chinese Medicine 10, 303, 547 tramadol 102, 104, 141, 142, 215, 240, 278, 283, 304, 313, 314, 315, 321, 324, 344, 352, 354, 386, 549 transcutaneous electrical nerve stimulation 71, 115, 116, 164, 194, 202, 215, 242, 246, 247, 278, 283, 303, 555, 561 transcutaneous electrical nerve stimulation, in angina 283 transdermal fentanyl 104, 141, 143, 145, 316, 353 transdermal opioid 143, 490 transdermal PCA fentanyl 108 transdermal theraupeutic system, Catapres TTS 399 transforaminal approach 188, 460 transmyocardial revascularization 283, 284 transsacrococcygeal ligament 448 trauma patient, treatment of pain 112 treatment manual for the patient 615 tricyclic antidepressant 102, 141, 145, 163, 175, 185, 193, 240, 243, 293, 305, 330, 340, 379, 393, 545 trigeminal autonomic cephalalgias 158 trigeminal nerve, mandibular branch 183, 186, 191

trigeminal nerve, maxillary branch 173, 186, 190, 419, 432, 433 trigeminal nerve, ophthalmic branch 183, 186, 190 trigeminal nerve, radiofrequency thermocoagulation 172, 410 trigeminal neuralgia 144, 157, 158, 160, 172, 181, 190, 192, 231, 237, 240, 305, 384, 386, 396, 409, 411, 433, 434, 440, 511, 514, 519, 548 trigeminal neuralgia, atypical 183 trigeminal root entry zone 182, 512, 514 trigger for migraine 163 trigger point injection 170, 175, 176, 194, 202, 408, 556 trigger Points 161, 175, 194, 200, 228, 229, 230, 398, 408, 409, 551 triptans 166, 167 Trp allele, frequencies 56 tsun 551 TTS see therapeutic transdermal system tumour necrosis factor-alpha 263, 268 tunnelled catheter-external pump system 476 Tuohy epidural needle 504 ulnar nerve 244, 269, 421, 422, 427, 585 ultrasound machine 406, 423, 424 ultrasound scanning guided technique 435 ultrasound treatment 561, 562, 565 ultrasound, imaging for procedures 318, 406, 423, 424, 427, 435, 445 unidimensional scales, sensitivity of 24 unidimensional scales, uni-dimensional scales 11, 19, 20, 24, 73, 137 unipolar leads 501 upper gastrointestinal cancer 439 upper thoracic chain 442 ureteric strictures 443 uric acid lowering agents 267 uricase 267 uricosurics 267 valdecoxib 100, 369, 371 validity 12, 19, 24, 25, 26, 39, 46, 77, 227, 229, 313, 357, 464, 604, 608, 609 validity and reliability, of unidimensional scales 24 VALPAR 575, 576, 577 VALPAR Component Work Samples 575, 576 valproate 166, 169, 243, 330, 384 valuing 595 vanilloid receptor-1 (TRP-V1) 239 vanilloid receptors 4, 439 variability 24, 46, 53, 65, 72, 73, 104, 116, 208, 301, 312, 316, 382, 441, 606 VAS see visual analogue scale vascular compression theory 182 vascular thrombosis 257 vascular ulcers 439, 442 VCWS see VALPAR Component Work Samples venlafaxine 278, 381, 382, 383, 387

Index 635

venous thrombosis 117 ventralis posteromedialis 519 ventropostero-lateral nucleus 519 verapamil 166, 168, 173 verbal descriptive scales 96 verbal rating scale 19, 22, 26, 137 verbal rating scale see verbal rating scale vertebroplasty 214, 459, 470, 532 vibrameter 42, 45 Virchow’s triad 279 visceral pain 292, 340, 439, 444, 467, 475, 517 visceral pain in gastro-intestinal cancer 439 visual analogue scale 19, 20, 73, 78, 96, 118, 137, 138, 202, 304, 313, 554 visual numeric rating scales 96 vocational counseling 574 von Frey 11 von Frey hairs/Semmes-Weinstein Monofilaments 45 VPL see ventropostero-lateral nucleus VPM see ventralis posteromedialis

Western Ontario and McMaster Universities Osteoarthritis index 555 whiplash injury 199, 202, 412, 413 whiplash-associated disorders 202 WHO defined palliative care see palliative care, WHO definition wide dynamic range neurons 5, 223, 399 wide-field radiotherapy 529, 530 wind up 5, 222, 227, 397 Wisconsin Brief Pain Inventory 20, 23 WOMAC see Western Ontario and McMaster Universities Osteoarthritis index Wong-Baker Faces Pain Scale 313 work hardening program 574, 576, 577 work role 574, 576, 577 workplace related factors 539

WAD see whiplash-associated disorders Waldman and Coombs, spinal delivery device classification 146 Wallerian degeneration 148, 407 Water Tai Chi, Water Yoga and Water Pilates 565

ziconotide 147, 406, 407, 478, 479 ziconotide, intrathecal 478 zoledronic acid 145 zostrix 400 zygapophyseal joints 461, see facet joints

xanthine oxidase inhibitors yellow flags yin-yang

267

51, 212