Pain: The Person, the Science, the Clinical Interface

PAIN

PAIN

The Person, the science, the clinical interface

Edited by Patricia Armati

with Roberta Chow

IP COMMUNICATIONS

Melbourne 2015

IP Communications, Pty. Ltd.,

PO Box 1001

Research, Victoria, 3095

Australia.

Phone: +61 0423 269 353

E-mail: ipcomm@bigpond.com

www.ipcommunications.com.au

© Patricia Armati with Roberta Chow

Authors retain copyright for their contributions to this volume

First published 2015

This book is copyright. Subject to statutory exemption and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of IP Communications, P/L.

ISBN: 978-0-9872905-6-4

National Library of Australia Cataloguing-in-publication data

Title: Pain: the person, the science, the clinical interface/Patricia Armati, Roberta Chow, editors

ISBN: 9780987290564 (paperback)

Notes: Includes bibliographical references and index.

Subjects: Pain—Diagnosis.

Pain—measurement.

Pain—Treatment.

Pain—Social aspects.

Pain—Psychological aspects.

Other Creators/Contributors: Armati, Patricia J., editor.

Chow, Roberta T., editor.

Dewey Number: 616.0472

Edited by Gillespie & Cochrane, Pty. Ltd., Melbourne

Text design by Club Tractor Production Services, Melbourne

Typeset by Desktop Concepts Pty. Ltd., Melbourne

Cover design by Anne-Marie Reeves, Melbourne, based on an illustration by Ben Roediger, Sydney

Indexed by Mary Russell, Melbourne

Printed by BPA Print Group, Pty. Ltd., Melbourne

Contents

Guide to colour plates

Preface

Acknowledgements

Foreword

About the editors

About the authors

Section 1    The person

Chapter 1      Pain and the front line – a general practitioner’s perspective

Roberta T Chow

Chapter 2      Understanding the pathophysiology of pain

Philip J Siddall

Chapter 3      Myofascial pain

Peter T Dorsher

Chapter 4      The management of acute pain

Ian Mowat, Elystan Hughes, and Stephan A Schug

Chapter 5      Postoperative pain

David A Scott and Pamela E Macintyre

Chapter 6      Transition from acute to chronic neuropathic pain: potential new players on the horizon

Joshua E Adler, Amy Hinkle, and Anne M Skoff

Chapter 7      fMRI and pain

Mark C Bicket and Paul J Christo

Chapter 8      Migraine and other primary headache disorders

Peter J Goadsby

Chapter 9      Neuropathic pain

Philip J Siddall

Chapter 10    Pain management in cancer patients

Muhammad Salman Siddiqi and Paul Glare

Chapter 11    Pain in children and adolescents

Matthew Crawford, Tamara Lang, Hsuan-Chih Lao, and David Champion

Section 2    The science

Chapter 12    Opioids and their signalling mechanisms at opioid receptors

Macdonald J Christie

Chapter 13    Gates and other theories of pain

Lucy A Bee and Anthony H Dickenson

Chapter 14    Neuroinflammation, TNF, and pain

Kinshi Kato, Veronica I Shubayev, and Robert R Myers

Chapter 15    Skin, neurons, neuroglia, and pain

Patricia J Armati

Section 3    The clinical interface

Chapter 16    The biopsychosocial model of chronic pain

Tony Merritt, Louise Sharpe, and Jade Hucker

Chapter 17    Psychological approaches to chronic pain

Tony Merritt, Louise Sharpe, and Jade Hucker

Chapter 18    Integration of primary care into the management of chronic pain

Geoffrey Mitchell

References

Index

Guide to colour plates

Plate 1     The process of inflammation and peripheral sensitisation indicating the chemicals involved in the ‘sensitising soup’ released following trauma.

Plate 2     Expression of sodium and calcium channels following nerve injury.

Plate 3     Development of ectopic activity in primary afferents following nerve injury.

Plate 4     Cellular processes involved in central sensitisation within dorsal horn neurons.

Plate 5     Structures and chemicals involved in pain modulatory pathways.

Plate 6     Brain processes involved in the perception of and response to pain.

Plate 7     Biological processes involved in the experience of pain.

Plate 8     Example of a myofascial trigger point and its referred pain pattern.

Plate 9     Pathophysiology of migraine

Plate 10   Activations identified on PET in migraine.

Plate 11   Activations on PET in the region of the posterior hypothalamic grey matter in patients with acute cluster headache (A) and paroxysmal hemicrania (B).

Plate 12   A. Morphine, a seemingly high intrinsic efficacy agonist, produces perhaps 50% of the μ receptor stimulus (G protein activation) compared with the highest intrinsic efficacy agonists known.

B. Low intrinsic efficacy opioids such as buprenorphine have a much lower μ receptor stimulus than morphine, but produce good analgesia in opioid-naive individuals.

Plate 13   A. Diagram of human skin showing organisation of the strata which are selectively innervated by C fibre subsets

B. Immunostained human skin biopsy showing C fibre endings in the epidermis.

Plate 14   Nodal area of rat nerve fibres immunostained with antibody to axonal neurofascin.

Plate 15   Diagram of nervous system response to nociceptive pain.

Preface

The person with pain is the centrepiece of this book. At some time, every person experiences pain; pain is part of the human experience and as old as humanity. It is a signal that demands attention.

Pain cannot be seen, cannot be heard, and cannot be touched or measured. This means that assessing, diagnosing, and treating each person’s pain is a very personal and individual experience. A person’s pain can lead to a tsunami of events at the personal and professional level, while a single painful event rarely affects only the person.

To emphasise the personal and individual nature of pain and its flow-on dilemma at all levels – the person, their families, friends, communities, villages, and the health budget of all countries – this book is organised so that the person with pain remains the focus and the recurrent theme.

The possibility of personalised pain treatment should hold great hope in the not-too-distant future. Personalised pain regimes will be able to assess underlying pathophysiology, genetics, phenotypic variation, and probably factors as yet undefined. Ultimately, pain involves the nervous system and interpretation of the phenomenon of pain at the cortical level. As the functional complexity of the human nervous system is revealed, and in concert with the BRAIN initiative of US President Obama <www.whitehouse.gov/share/brain-initiative>, the person in pain of the future may look forward to improved treatment. The chapter on fMRI provides a basis for this optimism.

We are delighted to have assembled an international team of experts in their fields and we thank all the many authors who spent so many hours of their valuable time to contribute their chapters. To all of you – thank you. To the many experts and colleagues who read and commented on the chapters, we are very grateful, and each is acknowledged below.

The hope is that this book will provide a different and useful focus from most pain books, and that the information is relevant and of use for pain teams, medical specialists, psychologists, nurses, physiotherapists, and other health professionals.

The book is organised in three sections – The Person; The Science; and The Clinical Interface. Chapters have been edited to present information in an international context. The theme of the National Pain Strategy document for Australia 2010 has provided a roadmap. Chapters may be read individually or the book may be read cover-to-cover. Between each of the three sections is a short linking statement to ensure the focus is on the person in pain. Some chapters have a ‘Recommended Reading’ list. The websites and recommended reading will be updated from time to time on the Brain and Mind Research Institute, Nerve Research Foundation, University of Sydney website: www.usyd.edu.au/nrf.

This diagram represents the complex and dynamic interactions between the person in pain, their relationships with family/carer, the community, and with medical professionals at all levels. Illustration: Ben Roediger

Patricia Armati, Editor, with Roberta Chow

January, 2015

Acknowledgements

The editors would like to thank the following people for their advice and, in many cases, for reviewing chapters:

Professor John Pollard MBBS BSc(Hons) FRACP FRCP (Lond), AO,

Professor Michael Boyer MBBS, AM

Dr Stanley Jacobson MBBCh

Dr Emily Mathey BSc(Hons) PhD

Dr Andrew Pembroke MBBS FANZCA

We also thank Jill Henry, the Commissioning Editor, who was always available to answer our questions, endlessly encouraging, unfailingly helpful and always calm, and Elizabeth Pigott and Jeremy Cullis, Medical Science Faculty Liaison Librarians, University of Sydney. And finally, everyone needs a secret weapon – ours was Christine Box, who remained unfazed by anything.

Foreword

Professor Michael J Cousins AO

MB BS MD DSc(Syd Uni) DSc(Hon McMaster Univ) FANZCA FRCA FFPMANZCA FAChPM(RACP) FFPMCAI(Hon) FAICD

Professor and Head of Pain Management Research Institute

Kolling Institute, University of Sydney at Royal North Shore Hospital

Board Member, Painaustralia

As far as I know, this book represents the first collaboration between a professor of neuroscience (Patricia Armati) and a general practitioner/researcher (Roberta Chow). Thus, it comes as no surprise that the very first chapter describes general medical practice as ‘the frontline of pain management’. Few would argue with this proposition. Indeed, at the National Pain Summit of Australia (2010), a National Pain Strategy, supported by 150 healthcare and consumer organisations, placed the primary care level as key to advancing pain management. Subsequently, National Pain Strategies developed in Canada, the United Kingdom, the United States, and Europe have given similar emphasis to primary care.

In Australia, a key step in implementing the National Pain Strategy has been formation of the advocacy body, Painaustralia, with a Board consisting of consumers and health professionals. Initiatives by state and Federal governments have been fostered by Painaustralia. All of these have emphasised the urgent need for education at all levels: community, undergraduate health professional curricula, specialist curricula, and primary, secondary, and tertiary levels of health care. Compared with the size of the healthcare problem posed by under-treatment of pain, the educational content devoted to pain in all settings is woefully inadequate; however, encouraging steps are now being taken. This enormous unmet need for education programs has been communicated to Painaustralia. One response has been a web-based Pain Education Program developed by a collaboration between the Royal Australian College of General Practitioners and the Faculty of Pain Medicine of the Australian & New Zealand College of Anaesthetists (ANZCA). This textbook is also an important primary care–oriented pain education initiative.

Chronic pain is an extraordinarily complex field, with exciting advances in scientific knowledge, which extend down to the cellular, subcellular, and genetic levels, and up to clinical, epidemiological/population health levels, as well as to translational research/development. Thus, this text presents a sample of some of the ‘science’ (see chapters 2, 12–15) that currently seems to have the most application for clinical care, particularly at the primary care level. It is very important that the science of pain advances rapidly, since the clinician is currently hampered by significant gaps in understanding of pain mechanisms, and has too few really effective ‘tools’ to treat pain. In particular, powerful pharmacological and non-pharmacological options are needed to prevent transition from acute to chronic pain (see chapters 4–6) after injury, surgery, or other ‘medical conditions’ such as acute radicular pain. Herein lies a very large opportunity for preventive medicine.

When one takes into account the current under-treatment worldwide of acute, chronic, and cancer pain, and associated costs to individuals, families, and the community, it is clear that pain is now the third most costly healthcare problem. It is costly because of the suffering of people in pain and because of the huge financial costs (over $34 billion per year in Australia, with a population of just over 20 million). Indeed, pain now should justifiably be a National Health Care Priority. In this context, an up-to-date text is a valuable education tool focusing on the key primary care level.

Education is crucial to improved pain management. However, a major stimulus is needed to open the eyes of the community, governments, and health professionals to the plight of those millions of people worldwide who often suffer in silence. The International Pain Summit and its key outcome, The Declaration of Montreal, has provided at least part of such a stimulus. The Declaration says in part: ‘Access to Pain Management is a fundamental human right’ (Cousins and Lynch 2011).

Subsequently, the World Medical Association has strongly supported the message of the Declaration, as has the International Federation of Health and Human Rights Organisations (IFHHRO).

Such unprecedented events place even more emphasis on the need for a major new focus on education for all health professionals providing care for people in pain.

REFERENCES

Cousins MJ, Lynch ME (2011) Declaration of Montreal: access to pain management is a fundamental human right. Pain 152, 2673–2674.

Cousins MJ (2013) Unrelieved pain: a major health care priority. Med J Aust 196, 372–373.

National Pain Summit of Australia (2010) National Pain Strategy – Australia. www.painaustralia.org.au.

About the editors

Patricia J Armati (BSc MSc PhD) is Honorary Professor in Neuroscience in the Central Clinical School, University of Sydney, and Mind and Brain Institute of the University of Sydney, with a long-standing interest in the relationship between neurons and neuroglia. She has published over 100 scientific papers and book chapters and is editor of The Biology of the Schwann Cell (Cambridge University Press, 2007), The Biology of Oligodendrocytes (Cambridge University Press, 2010), and Marsupials (Cambridge University Press, 2006), the first textbook on marsupials. She has been a board member of the International Peripheral Nerve Society and an editorial board member of the Journal of the Peripheral Nervous System. Currently, she is an editor of the Journal of Neurolipids.

Roberta T Chow (MBBS (Hons) FRACGP PhD) is a general practitioner in private practice in Sydney, Australia, specialising in pain medicine at a primary-care level. During the course of her general practice, she has developed a special interest in pain medicine, with a diploma from the Pain Management and Research Centre, Royal North Shore Hospital, Sydney, and a PhD from the Faculty of Medicine, University of Sydney, that focused on a clinical trial of neck pain. She is an Honorary Research Associate at the Brain and Mind Institute at the University of Sydney, President of the Australian Medical Laser Society, and has been a member of the Steering Committee for development of the Australian National Pain Strategy, a guide to integrated and innovative planning for pain management across Australia.

Dr Chow uses both orthodox and complementary therapies, particularly low-level laser therapy and acupuncture, for pain management.

About the authors

Joshua E Adler (MD PhD) received his postgraduate training in Neurology at New York Hospital-Cornell University Medical Center. Following residency, he served a post-doctoral fellowship under Dr Ira Black and then joined the faculty at Cornell. His research focused on novel neurotrophic factors and pain-related peptides such as substance P and somatostatin. He is Associate Professor, Neurology, Wayne State University, based at the Detroit Veterans Administration Medical Center in Detroit, providing clinical service and research. He is also Section Chief of Pain Management. He is currently working on an in vivo model of neuropathic pain that is considering both pathophysiologic mechanisms and potential novel modes of therapy.

Lucy A Bee (BSc PhD) was an Associate Faculty Member of the Department of Neuroscience, Physiology and Pharmacology, University College, London. Dr Bee was concerned with investigating the sensory role of the brainstem rostral ventromedial medulla zone in normal and pathophysiological states, and in particular the part played by facilitatory neurons. This is achieved by pharmacologically manipulating neurons in the rostral ventromedial medulla and looking at the evoked responses of dorsal horn neurons in the spinal cord to a range of stimuli after nerve injury. More recently, she investigated the roles of ion channels in different pain states. She is currently a medical writer in health care.

Mark C Bicket (MD) is currently Chief Resident in the Department of Anesthesiology and Critical Care Medicine at the Johns Hopkins University School of Medicine, Baltimore. He has worked with the American Society of Anesthesiologists, American Society of Regional Anaesthesia and Pain Medicine, and Health Volunteers Overseas.

David Champion (MB BS MD FRACP FFMANZCA) is Honorary Research Associate, Department of Anaesthesia and Pain Medicine, Sydney Children’s Hospital, Randwick, New South Wales, and Associate Professor, School of Women’s and Children’s Health, University of New South Wales, Kensington. After a career in adult and paediatric rheumatology and pain medicine, he is now focused primarily on paediatric pain research. His publications in this field range widely from measurement and assessment, including the internationally applied Faces Pain Scale, through somatosensory testing, pain-related psychology, acute and chronic pain, to therapeutics. Currently, his major project is a twin family case-control study on the heritability and associations, including potentially causal influences, of the common pain disorders without disease.

Macdonald J Christie (BSc (Hons) PhD) is Professor of Pharmacology and Associate Dean, Research, in the Sydney Medical School, University of Sydney, Australia. He was awarded his PhD in 1983 and then worked as a Fogarty International Fellow at MIT and the Vollum Institute in Oregon before being appointed as a continuing academic at the University of Sydney in 1990. He has been a Senior Principal Research Fellow of the National Health and Medical Research Council (NHMRC) since 2003. Prior to this he was a Medical Foundation Senior Principal Research Fellow from 1998 to 2002. He has served on numerous editorial boards, NHMRC grant committees, and NHMRC Academy since the mid-1990s. He has published over 200 peer reviewed research papers that have received more than 11 000 citations. His interests span cellular, molecular, and behavioural neuropharmacology, the biological basis of adaptations producing chronic pain and drug dependence, and preclinical development of novel pain therapeutics.

Paul J Christo (MD MBA) is a board certified, Harvard-trained anaesthesiologist and Johns Hopkins-trained pain medicine specialist. He directed the Multidisciplinary Pain Fellowship Program at the Johns Hopkins Hospital, and directed the Blaustein Pain Treatment Center at Hopkins. Dr Christo is an invited lecturer both nationally and internationally, serves on two journal editorial boards, has published more than 60 articles and book chapters, co-edited three textbooks on pain, and teaches medical students, residents, and pain fellows. He has been a course director or coordinator for many continuing medical education programs that focus on educating specialists and generalists on important aspects of pain diagnosis and treatment.

Matthew Crawford (MB BS FANZCA FFPMANZCA FCICM) is Director of Pain and Palliative Care at the Sydney Children’s Hospital, Randwick, New South Wales, and is Senior Staff Specialist in Anaesthesia and Intensive Care, and Clinical Director of the Surgery and Anaesthesia Programs at Sydney Children’s Hospital. He has a particular interest in post-operative and chronic pain management in children. He has provided paediatric anaesthetic and intensive care services in a voluntary capacity for many South Pacific islands, Myanmar, and Rwanda. He has a research interest in physiology, anaesthesia, and intensive care procedures, and has published in international journals.

Anthony H Dickenson (BSc PhD FMedSci FBPharm) is Professor of Neuropharmacology in the Department of Neuroscience, Physiology and Pharmacology at University College, London, with a PhD at the National Institute for Medical Research, London. He has held posts in Paris, California, and Sweden. His research interests are pharmacology of the brain, including the mechanisms of pain and how pain can be controlled in both normal and pathophysiological conditions, and how to translate basic science to the patient. He is an Honorary Member of the British Pain Society, a Fellow of the British Pharmacological Society, and a founding and continuing member of the London Pain Consortium. With his research team he has authored more than 290 refereed publications, and he has made many media appearances.

Peter T Dorsher (MS MD) is Chair, Physical Medicine and Rehabilitation, Mayo Clinic, Florida, and was Assistant Professor, Physical Medicine and Rehabilitation Residency, Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, from 1985 to 1989. He attended medical school at Rush Medical College, Chicago, and obtained his Masters of Science, Biomedical Engineering, from Northwestern University, Evanston, Illinois, and Bachelors of Science, Biomedical Engineering, at Case Institute of Technology, Cleveland, Ohio. He has made numerous regional, national, and international presentations on myofascial pain, chronic pain, acupuncture, and their relationships. He has published over 30 journal articles, six book chapters, one book, and 20 miscellaneous publications on neurologic disorders, fibromyalgia, chronic pain, and Eastern medicine. He is currently working on development of the Mayo Spine Center for care of spine disorders.

Paul Glare (MBBS MA MMed) is Chief of the Palliative Medicine Service and Attending Physician in the Department of Medicine at Memorial Sloan Kettering Cancer Center (MSKCC), New York. He is also Professor of Medicine at the Weill Cornell Medical College. He has published more than 70 peer-reviewed articles on pain and palliative care, and more than 20 book chapters. He is the editor of textbooks on opioid pharmacology and on prognostication, both published by Oxford University Press. He is also an Associate Editor of the textbook Palliative Medicine, published by Elsevier in 2008.

Peter J Goadsby (MD, PhD UCSF) obtained his basic medical degree and training at the University of New South Wales, Australia. His neurology training was done with Professor James W Lance in Sydney. After post-doctoral work in New York with Don Reis at Cornell, with Jacques Seylaz at Université VII, Paris, and postgraduate neurology training at Queen Square, London, with Professors C David Marsden, Andrew Lees, Anita Harding, and W Ian McDonald, he returned to the University of New South Wales and the Prince of Wales Hospital, Sydney, as a consultant neurologist and Associate Professor of Neurology. He was appointed a Wellcome Senior Research Fellow at the Institute of Neurology, University College, London in 1995. He was Professor of Clinical Neurology and Honorary Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square, London, until 2007. At the time of writing he was Professor of Neurology and Director of the Headache Center, Department of Neurology, University of California, San Francisco, but is currentlyProfessor of Neurology, King’s College, London, and Director, NIHR-Wellcome Trust Clinical Research Facility, King’s College Hospital, London. He is an Honorary Consultant Neurologist at the Hospital for Sick Children, Great Ormond St, London, and in the Department of Neurology, University of California, San Francisco, and Chair of the British Association for the Study of Headache.

Amy Hinkle (MSc) holds a Master of Science from Wayne State University School of Medicine, United States, with a focus in neuroscience. She has ten years of research experience in industry and academia. Her early start working in a biochemistry lab at Oakland University at the age of 15 propelled her to a career as a Research & Development scientist at Oxford Biomedical Research. After completing undergraduate degrees in Biochemistry and Applied Mathematics at Oakland University, she moved on to complete her graduate program at a young age. Her primary interests in genetics and neuroscience stem from a family history of migraines and Complex Regional Pain Syndrome.

Jade Hucker (BSc(Hons) MPsychol (Clin) (Hons)) is a clinical psychologist dedicated to work in the field of chronic conditions including chronic pain. She currently works at the Royal Prince Alfred Hospital Pain Management Centre, Camperdown, New South Wales, where she is responsible for clinical psychology services. She has extensive experience delivering individual and group-based programs for people with chronic pain, and provides education to other health professionals on managing chronic pain. Jade is also a Clinical Associate of the University of New South Wales, and a supervisor of Intern Clinical Psychologists.

Elystan Hughes

Elystan Hughes (BSc(Hons) MB BCh FRCA) is a Senior Registrar based at Queen Elizabeth Hospital, Birmingham, United Kingdom. Originally from West Wales, he studied Biochemistry at Imperial College, London, and Medicine at Cardiff University. Specialising in anaesthesia, his interests include acute pain management, trauma, and regional anaesthesia. He has undertaken Research and Regional Anaesthesia fellowships in Australia. Currently based in the United Kingdom, Dr Hughes works internationally and contributes to advancement of high quality pain management strategies.

Kinshi Kato (MD PhD) is a spine surgeon and Assistant Professor in the Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. He received his medical education and surgical training from Fukushima Medical University, and additional post-graduate education in molecular biology at the Peripheral Nerve Research Group in the Department of Anesthesiology, University of California, San Diego, United States. He now specialises in spine surgery and sports medicine, with a special interest in lumbar disorders, and received the Best Paper Award at the annual meeting of the International Society for the Study of the Lumbar Spine (ISSLS). His clinical and research interests include neuropathic pain, cytokines in neuroinflammation, psychosocial factors in chronic low back pain, primary care for low back pain in athletes, and minimum invasive lumbar surgery for athletes.

Tamara Lang (BPsychol (Hons) MPsychol (Clin) (Hons) DPhil) is a clinical psychologist specialising in children and adolescents. She has a Masters of Clinical Psychology from the University of New South Wales, and gained a Doctor of Philosophy at the University of Oxford, United Kingdom. Tamara works with children, adolescents, and their families requiring psychological assessment and treatment for a broad range of issues, such as chronic pain, depression, anxiety, stress, challenging behaviours, grief, loss, and social problems. She is currently working in the pain and palliative care team at Sydney Children’s Hospital, and is a Conjoint Lecturer in the Faculty of Medicine, University of New South Wales.

Hsuan-Chih Lao (MD MSc) has been a senior supervising doctor in the Anaesthesia and Pain Department in Mackay Memorial Hospital, Taipei, Taiwan. She specialises in obstetric and paediatric cardiovascular anaesthesia and interventional pain management. Previous research has been related to labour analgesia and heart rate variability. She is a research fellow in the Pain and Palliative Care Department, Sydney Children’s Hospital, Australia, having completed the fellowship training program for adult pain management. She is also a lecturer in the Medical School of National Yang-Ming University, Taiwan, and Director of resident training programs in the department. Her current interest is pain management for children with autoimmune disease.

Pamela E Macintyre (BMedSci MBBS MHA FANZCA FFPMANZCA) is an Associate Professor and Director of the Acute Pain Service at Royal Adelaide Hospital, South Australia, since it was established in 1989, the first such service in Australasia and one of the first in the world. She is a Foundation Fellow of the Faculty of Pain Medicine, Australian and New Zealand College of Anaesthetists, and an examiner for the Faculty. Her key areas of interest have been management of acute pain in more complex patients, safety of and education about acute pain management, and improving acute pain management practices in hospitals and after discharge. She has co-authored one and co-edited another book on acute pain management, co-authored a number of chapters and papers, and was senior editor for the second (2005) and third (2010) editions of Acute Pain Management: Scientific Evidence, published by ANZCA and the FPM.

Tony Merritt (BA(Hons) MPsychol (Clin) (Hons) MAPS) is a clinical psychologist working in private practice in Sydney, Australia, and runs Sydney Clinical Psychology. He is an Associate Lecturer in the Masters of Clinical Psychology program at the University of New South Wales, and a clinical supervisor and clinical associate at the University of New South Wales, Macquarie University, and University of Sydney. He supervises many intern and qualified clinical psychologists.

Tony has worked across various public and private services, including Royal Prince Alfred Hospital Pain Management Centre, St Vincent’s Hospital Gambling Treatment Service, and Prince of Wales Private Hospital. At the Black Dog Institute, Australia, Tony runs workshops on workplace mental health, professional development training for general practitioners, professional development training for mental health professionals on medications, and Bipolar Disorder.

Geoffrey Mitchell (MBBS, PhD FRACGP FAChPM) is Professor of General Practice and Palliative Care at the University of Queensland, and Head of the MBBS program at Ipswich. His main research interest is the role of general practitioners in palliative care, cancer in general, and complex conditions. Current research includes interventions to improve outcomes for caregivers for people with advanced cancer, health services research in palliative care and primary care, and single patient trials. He has published over 150 peer-reviewed publications. He has been a chief investigator on over $16 million of National Health & Medical Research Council, Australia, funding. He maintains a clinical general practice in Ipswich, Queensland, Australia.

Ian Mowat (MA, MBBS, FRCA, EDRA) is an Anaesthetic Specialty Registrar with interests in regional anaesthesia, pre-operative assessment, peri-operative management, and acute pain. Educated at Cambridge University and Guy’s, King’s and St Thomas’ School of Medicine, Dr Mowat is currently a trainee in the St George’s School of Anaesthesia, London. His chapter was written during placement as an Anaesthetic Research Fellow at Royal Perth Hospital, Western Australia.

Robert R Myers (PhD) is Professor Emeritus in the Departments of Anesthesiology and Pathology at the University of California, San Diego. His academic training is in bioengineering and neurosciences, and his principal interests are in the pathogenesis of neuropathic pain, particularly the role of cytokine mechanisms of nerve injury and pain. Other interests include the neurotoxicity of local anaesthetics, the neurophysiology of microcirculation, and the integrative pathophysiology mechanisms in nerve and spine injury that cause pain. He has led the Peripheral Nerve Research Group at University of California, San Diego, for many years, has been Editor-in-Chief of the Journal of the Peripheral Nervous System, and has trained international scholars in neurobiology, orthopaedics, and neurology.

Stephan A Schug (MD FANZCA FFPMANZCA) is currently Professor and Chair of Anaesthesiology in the Pharmacology and Anaesthesiology Unit of the University of Western Australia, and Director of Pain Medicine at Royal Perth Hospital, Australia. Professor Schug is a German-trained specialist anaesthetist with an MD in pharmacology. He has previously worked at the University of Cologne, Germany, and then was Chair of Anaesthesiology at the University of Auckland in New Zealand.

His main research interests are in the pharmacology of analgesics and local anaesthetics, the management of acute, chronic, and cancer pain, regional anaesthesia and analgesia, organisational structures for pain management, and reduction of adverse events in hospitals.

Professor Schug has over 350 publications, including peer-reviewed journal articles, books, and book chapters, mainly in the areas of regional anaesthesia and acute and chronic pain management. Professor Schug is often invited to present at national and international conferences.

David A Scott (MB BS PhD FANZCA FFPMANZCA) is Associate Professor and Director of Anaesthesia at St Vincent’s Hospital in Melbourne, Australia. He was Director of the Acute Pain Service at St Vincent’s from its inception in 1990 until 2010. He has clinical and research interests in a wide range of areas, including regional anaesthesia and acute pain management, and has researched and published extensively in these areas, including a number of book chapters. His other interests include the long-term cognitive impacts of anaesthesia. He completed a PhD on neuropathic pain in 2004. He is especially interested in the safety and outcomes related to acute pain management.

Louise Sharpe (BA(Hons) MPsych PhD) is a Professor of Clinical Psychology in the School of Psychology, University of Sydney, Australia, and is a Senior National Health and Medical Research Council (NHMRC) Research Fellow. She completed her undergraduate and clinical training at the University of Sydney, and has a PhD from the University of London. She is an expert in health psychology and the development and evaluation of novel interventions for patients with a range of health problems, and has particular expertise in the management of chronic pain. She has been the recipient of over $3.5 million in competitive grant funding, with current funding from the Australian Research Council and NHMRC, and has published more than 120 peer-reviewed journal articles, including the results of nine randomised controlled trials of psychosocial interventions.

Veronica I Shubayev (MD) is Associate Professor of Anesthesiology at the University of California, San Diego, United States, and Research Physiologist at the Veterans Affairs San Diego Healthcare System. She studies the role of immune responses associated with peripheral nerve injury in axonal regeneration, phenotypic changes and survival of Schwann cells and their remodelling, including the compact myelin lamellae, and functional recovery of peripheral nerve following damage or disease. Among her significant scientific contributions is the discovery of axonal transport of inflammatory cytokines, providing a mechanism of central neuroinflammation and neuropathic pain after peripheral lesions, and the work implicating matrix metalloproteinases (MMPs) and myelin basic protein as novel classes of pain mediators.

Philip J Siddall (MBBS MM (Pain Mgt) PhD FFPMANZCA) is Director of the Pain Management Service at Greenwich Hospital in Sydney and Conjoint Professor in Pain Medicine at the University of Sydney, Australia. He spent three years in China studying acupuncture, after which he completed a PhD in pain physiology at the University of Sydney. He currently combines clinical pain medicine with research into the mechanisms and management of pain. His research interests are in the area of neuropathic pain, particularly following spinal cord injury, as well as the role of modulatory pathways and spiritual and existential issues in pain.

Muhammad Salman Siddiqi (MD) was born and raised in Pakistan. He managed to secure merit scholarships in different examinations in his childhood, and graduated in medicine from the Rawalpindi Medical College, Pakistan. After completing his internship and residency training in Pakistan, he worked in hospitals, including Shifa International Hospital, one of the most prestigious American hospitals in Pakistan. He moved to the United States in 1998 and worked as a clinical research associate on Alzheimer’s Disease and Zellweger Syndrome at Johns Hopkins Bayview Medical Center, Baltimore. For several years he was the appointed Senior Vice President in a healthcare management company in Rockville, Maryland, for all medical, regulatory affairs, and clinical development programs. He completed his residency in Neurology from the University of Toledo Medical Center in Ohio in 2012 and passed his Neurology Board from American Board of Psychiatry and Neurology. He joined Memorial Sloan–Kettering Cancer Center, New York, and completed fellowship training in Hospice and Palliative Care in 2013. He is currently a neurologist with a special interest in hospice and palliative care at Tallahassee Memorial Healthcare Hospital, Tallahassee, affiliated with Florida State University.

Anne M Skoff (BA MA PhD) received her Bachelors and Masters degrees in Biology from Boston University. She then received a doctorate in Molecular Immunology from Wayne State University, during which time she received several honours. Following her graduate studies, she worked in the laboratories of Drs Robert Lisak and Joyce Benjamins, studying the immunobiology of Schwann cells and their susceptibility to various cytokines. She joined Dr Adler’s laboratory in 1998 as Research Associate and has been responsible for many of the resulting behavioural and biochemical studies. Dr Skoff has been key in demonstrating the role of cytokines in secretion of nociceptive peptides.

Section 1

The person

The person in pain is the starting point for this first section of the book. It begins with a general practioner’s view of the complexity of pain presentation at the front line, where the doctor manages a spectrum of pain conditions. While this is generally accepted as primary care in developed countries, the World Health Organization (WHO) defines primary care more broadly in emerging and developing countries where pain is managed in very different sets of circumstances (www.who.int/topics/primary_health_care/en). The following chapters address the current understanding of the pathophysiology and treatment regimens of both acute and persistent pain.

Chapter 1

Pain and the front line – a general practitioner’s perspective

Roberta T Chow

INTRODUCTION

General practice is, in the main, the front line of pain management. It is at the clinical interface of general practice that a person in pain most commonly seeks treatment, where most people first enter the healthcare system, and where they return for ongoing management after acute hospital care (Review of Chronic Pain Management Advisory Group 2008; Starfield et al. 2005). General practice is where the science of pain medicine and the art of clinical practice intersect in a way that is different from that of a person in pain presenting to hospital or to specialists. This chapter discusses the problems and the complexity of pain medicine from the perspective of a GP at the front line.

One of the unique qualities and challenges of general practice is management of the diagnostic uncertainty of undifferentiated and evolving illnesses that have pain as the primary symptom. In this scenario, the person in pain comes to a general practitioner (GP) with a reasonable expectation of a diagnosis, appropriate investigation and treatment, including adequate pain relief. Such consultations with GPs occur by the millions worldwide, with predominantly positive outcomes. Nevertheless, behind this apparently simple scenario are layers of complexity that influence the person and the GP and can result in less than satisfactory long-term outcomes for many people in pain. Inability to address and manage these complexities, not only in general practice but also in the health system as a whole, underpins an epidemic of chronic pain, with costs of pain management measured in billions of dollars in industrialised countries (Access Economics 2007; Ekman et al. 2005; Lambeek et al. 2011; Wieser et al. 2011). Reasons for such an epidemic are complex and attributable to multiple factors. Howarth and colleagues consider it to be due to a failure in understanding the person in pain (Howarth et al. 2013), while Delpero suggests that it is the inadequacy of pain management guidelines (Delpero 2008). Turk and colleagues consider it to be a limitation in the translation of pain pathophysiology to effective treatments (Turk et al. 2011). Among the many problems are delays of months to years for referrals to tertiary level pain clinics (Lynch et al. 2007; Lynch et al. 2008) and an epidemic of iatrogenic opioid addiction (Garland et al. 2013; Ling et al. 2011; Manchikanti et al. 2012). These mounting problems have resulted in many people with pain seeking complementary and alternative therapies, which now play a large role at a primary care level (Rosenberg et al. 2008).

Given the challenges of optimal pain management, the longitudinal nature of ongoing care unique to general practice (Green and Holden 2003) can mitigate the sense of loss of control experienced by people in pain and reduce their powerlessness by reducing fragmentation in care (Andre et al. 2012). Keeping the focus on the person as an active participant and at the centre of care, rather than a passive receiver of care, is a marker of quality care (Lapsley 2012), and is at the heart of general practice as well as the focus of this book.

WHAT PAINFUL CONDITIONS DO GPS TREAT?

The first step in evaluating pain in general practice is to understand the nature and prevalence of pain in this clinical setting. The Better Evaluation and Care of Health (BEACH) and Supplementary Analysis of Nominated Data (SAND) studies, which evaluated 1.4 million GP consultations in Australian general practice, were among some of the earliest international studies to investigate this (Britt et al. 2008; Britt et al. 2010). These studies are particularly important, as general practice is identified as a critical intervention point for health care: about 83% of people visit a GP at least once a year. The data from these studies provide a basis for monitoring many aspects of public and individual health, including prevalence of diseases, assessing efficacy of treatment, and identifying potential strategies to improve outcomes. Britt and colleagues (2010) found a prevalence of 19.2% (95% CI = 17.4–21) for painful conditions, the third most common reason for people to visit a GP. Their pain was predominantly musculoskeletal, with 48% diagnosed as osteoarthritis, 29.2% as ‘back problems’, and 7.1% other forms of arthritis. Nearly one-third of people nominated ‘other condition’ as the cause of their chronic pain, of which 65.1% were musculoskeletal and 14.7% neurological. People with cancer-related pain constituted 2.4% of chronic pain consultations. These data are consistent with those of national (Blyth et al. 2003) and international population studies (Fitch and McComas 1985; Hoy et al. 2012), especially those related to low back pain. Such painful conditions are among the most common reasons for general practice consultations in many industrialised and non-industrialised countries (Murray et al. 2012).

THE CONSULTATION

Although epidemiological studies give a broad view of prevalence of pain nationally and internationally, in the face-to-face consultation with the GP a person in pain wants to know what is wrong with them, whether the condition is serious, and how the GP can most effectively treat the pain (Von Korff 1999). A person in severe pain is rarely interested in the science or the evidence, yet the treatment regime and even the language used by the GP at this early stage can have long-term consequences, both positive and negative. For example, early identification and management of risk factors for a person with back pain, such as catastrophising, can reduce progression of acute back pain to chronic (McGreevy et al. 2011, Weiner and Nordin 2010). Within that first consultation, therefore, the most important tool for the GP is effective communication (Elwyn et al. 2004), to establish a working diagnosis, but also to understand the person’s expectations, needs, and fears. Even the language used in the consultation can have a profound effect on the long-term outcome of the person’s pain (Darlow et al. 2013). Understanding the psychosocial elements of their pain will have the most important influence on therapeutic decisions and leads to improved outcomes (Huas et al. 2006; Müller-Schwefe et al. 2011).

Pain is a highly individual experience. How the person perceives the meaning of pain in the context of her or his past experience and within their family will modulate the intensity of pain. Coexisting anxiety or depression are also well known comorbidities with pain, and form part of the complex milieu of the psychosocial aspects of pain management (Gambassi 2009, Holmes 2012, Worz 2003). Furthermore, cultural and ethnic differences in the perception of the meaning of pain can add to the complexity of a person’s pain experience, and there is a need for nuanced management (Green et al. 2003a; Rahim-Williams et al. 2012).

The biopsychosocial aspects of a person’s pain that encompass all these elements are already present at the first GP encounter (Engel 1997; Lumley et al. 2011). The importance of the relationship between the GP and the person in pain in managing all these elements cannot be over-emphasised. It is the GP who has the advantage of understanding the context of the whole person and their personal situation and can therefore provide individualised care. Importantly, it is at this point in primary care that the first of the barriers that limit a person’s optimal pain management have been identified in the National Pain Strategy (NPS) of Australia (National Pain Summit of Australia 2010). (See also Chapter 17.) The NPS, an international first, brought together 150 representatives of professional organisations and patient advocates to systematically evaluate and find ways to overcome these and other barriers to better pain management. Canada followed with its first pain summit in 2012 (Canadian Pain Summit 2012), and other countries, such as the United States, are aware of the need for a national approach (Roehr 2011).

PAIN

To address one of the first barriers to effective pain management, there is a need to improve understanding of the nature of pain.

Pain is a complex clinical phenomenon that is still poorly understood across many domains of medicine. Over the last two decades, an exponential increase in pain medicine research has led to better understanding of the physiological and pathophysiological interaction between both peripheral nervous system (PNS) and central nervous system (CNS), the immune system, and the emotion milieu of the person which results in chronic pain. (See also chapters 7, 15, 16, 17.)

Until relatively recently, pain has been regarded as a secondary phenomenon caused by a primary pathology, and as something to be managed as a by-product of a disease. The Cartesian model proposes that if you treat the disease or the cause the pain will subside (Goldberg 2008). It is, however, now recognised that complex neurophysiological changes occur as a result of pain, whether it is caused by disease, injury, or surgery. Such change in thinking has led to the important concept of pain as a disease in its own right (Siddall and Cousins 2004). This then leads to a different management approach, directing the person in pain away from seeking a cure and towards optimising quality of life, even if pain persists. Strategies such as these are used in other chronic diseases, such as diabetes or asthma, and are applicable to chronic pain. Applications of new technology for examining systemic changes in the nervous system of a patient with pain, such as functional fMRI and near infrared spectroscopy (NIRS), provide a basis for the ‘pain as a disease’ model. These imaging techniques now demonstrate structural, though reversible, pain-induced changes in a number of brain areas, referred to as the ‘pain matrix’ (Iannetti and Mouraux 2010), rather than a single region of the brain. (See also chapters 7 and 11). Other studies relating to the pain matrix describe central sensitisation and wind up, which includes neural plasticity where the cells of both PNS and CNS, their neuroglia, the microglia of the brain and spinal cord, and the molecules that respond to and are modulated by nociceptive afferent stimulation (Apkarian et al. 2011, Coderre et al. 1993, Woolf and Salter 2000). (See also chapters 3 and 15.) The concept of pain as a disease is not universally accepted, however (Cohen et al. 2013). Cohen and colleagues (2013) suggest that it is a misinterpretation of current knowledge of pain pathophysiology and has the potential to obstruct more effective pain research. Cohen and colleagues do, however, acknowledge the critical importance of neuroplasticity and contextual aspects of a person’s pain. This clash of concepts has clinical implications for people in pain and GPs alike, when there is a need to reduce an unnecessary and potentially unhelpful