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Mission Statement of IASP Press速 The International Association for the Study of Pain (IASP) is a nonprofit, interdisciplinary organization devoted to understanding the mechanisms of pain and improving the care of patients with pain through research, education, and communication. The organization includes scientists and health care professionals dedicated to these goals. The IASP sponsors scientific meetings and publishes newsletters, technical bulletins, the journal Pain, and books. The goal of IASP Press is to provide the IASP membership with timely, high-quality, attractive, low-cost publications relevant to the problem of pain. These publications are also intended to appeal to a wider audience of scientists and clinicians interested in the problem of pain.


Central Neuropathic Pain: Focus on Poststroke Pain

Editors

James L. Henry, PhD Akbar Panju, MB, ChB, FRCP(C), FRCP(Edin), FRCP(Glasg) Kiran Yashpal, PhD Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada

IASP PRESS® • SEATTLE


© 2007 IASP Press® International Association for the Study of Pain® All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher. Timely topics in pain research and treatment have been selected for publication, but the information provided and opinions expressed have not involved any verification of the findings, conclusions, and opinions by IASP®. Thus, opinions expressed in Central Neuropathic Pain: Focus on Poststroke Pain do not necessarily reflect those of IASP or of the Officers and Councilors. No responsibility is assumed by IASP for any injury and/or damage to persons or property as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that there should be independent verification of diagnoses and drug dosages. Library of Congress Cataloging‑in‑Publication Data Central neuropathic pain: focus on poststroke pain / James L. Henry, Akbar Panju, Kiran Yashpal, editors. p.cm. Includes bibliographical references and index. ISBN 0-931092-66-3 (alk. paper) 1. Central pain. 2. Neuralgia. 3. Nervous system--Pathophysiology. 4. Pain-Treatment. I. Henry, J. L. (James L.) II. Panju, Akbar, 1949- III. Yashpal, Kiran, 1941­RC347.C46 2007 616.8'56--dc22

Published by: IASP Press International Association for the Study of Pain 111 Queen Anne Ave N, Suite 501 Seattle, WA 98109-4955, USA Fax: 206-283-9403 www.iasp-pain.org

Printed in the United States of America

2007061305


This book is dedicated to

Michael G. DeGroote whose generous support for pain research has made our dreams a reality


Contents List of Contributing Authors Preface Acknowledgments

ix xiii xiv

Part I Brain Trauma and Central Neuropathic Pain 1. Central Poststroke Pain: A Perspective James L. Henry, Kiran Yashpal, and Chitra Lalloo

3

2. Brief Historical Aspects of Central Poststroke Pain and a Case History of a Patient Suffering from this Condition Akbar Panju

7

3. Overview of Current and Emerging Therapies for Acute Stroke David J. Gladstone and Sandra E. Black

13

4. Clinical Characteristics of Central Poststroke Pain Henriette Klit, Nanna Brix Finnerup, and Troels S. Jensen

27

5. Central Pain in Stroke and Multiple Sclerosis: Similarities and Differences Jรถrgen Boivie

43

6. Correlates of Neuroplasticity in Poststroke Recovery Alexander Thiel, Birgit Schumacher, Carsten Eggers, Lutz Winhuisen, Walter F. Haupt,and Wolf-Dieter Heiss

55

Part II Pain Mechanisms 7. Mechanisms of Pain Barry J. Sessle

67

8. Mechanisms of Thalamic Pain A.D. (Bud) Craig

81

9. The Thalamus and Human Pain Jonathan O. Dostrovsky

101

Part III Neurological Changes Accompanying Neuropathic Pain 10. Pathophysiology of Central Poststroke Pain: The Contribution of Functional Imaging and a Hypothesis Kenneth L. Casey

115

11. Neuroimmune-Mediated Disinhibition: A Potential Mechanism for Central Poststroke Pain Yves De Koninck

133

vii


viii

contents

12. Brain-Derived Neurotrophic Factor in Central Nervous System Disorders and an Animal Model of Chronic Pain Monica Marchese, Qi Wu, James L. Henry, and Margaret Fahnestock

149

13. Central Poststroke Pain: An Animal Model James L. Henry

171

Part IV Approaches to Management of Central Poststroke Pain 14. Functional Imaging of Pain: A Cortical Model of Allodynia in Poststroke Pain and Fibromyalgia Anthony K.P. Jones and Alison Watson

183

15. Differential Diagnosis and Management of Pain after Stroke Angela Mailis Gagnon

211

16. Deep Brain Stimulation for the Alleviation of Poststroke Neuropathic Pain Sarah L.F. Owen, Alexander L. Green, John F. Stein, and Tipu Z. Aziz

219

17. Deep Brain Stimulation for Chronic Neuropathic Pain Clement Hamani, Jonathan O. Dostrovsky, Karen D. Davis, and Andres M. Lozano

229

18. Motor Cortex Stimulation in Central Poststroke Pain Benoit Pirotte, Philippe Voordecker, Danielle Baleriaux, David Wikler, and Marc Levivier

237

19. Suffering: Measuring the Immeasurable Beverley M. Clarke, A.R.M. Upton, and Claudia Castellanos

249

Part V Future Directions 20. Research Agenda: Looking Forward James L. Henry

263

21. Best Practice Guidelines for Treatment of Central Pain after Stroke Allan Gordon

267

Index

275


Contributing Authors Tipu Z. Aziz, MD, FRCS Department of Neurological Surgery, Radcliffe Infirmary, Oxford, United Kingdom Danielle Baleriaux, MD Department of Neuroradiology, ERASME Hospital, University of Brussels, Brussels, Belgium Sandra E. Black, MD, FRCPC Division of Neurology and Regional Stroke Centre, Sunnybrook Health Sciences Centre; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada Jörgen Boivie, MD, PhD Department of Neurology, University Hospital, Linköping, Sweden Kenneth L. Casey, MD Neurology Service, Veteran’s Affairs Medical Center, Ann Arbor, Michigan, USA Claudia Castellanos, BA(Hons), MCSE Neurology Division, Department of Medicine, McMaster University, Hamilton, Ontario, Canada Beverley M. Clarke, RPT, MSc School of Rehabilitation Sciences and Neurology Division, Department of Medicine, McMaster University, Hamilton, Ontario, Canada A.D. (Bud) Craig, PhD Atkinson Research Laboratory, Division of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA Karen D. Davis, PhD Division of Neurosurgery and Toronto Western Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada Yves De Koninck, PhD Division of Cellular Neurobiology, Robert Giffard Research Center, University of Laval, Beauport, Quebec, Canada Jonathan O. Dostrovsky, PhD Department of Physiology, University of Toronto, Toronto, Ontario, Canada Carsten Eggers, MD Clinic for Neurology, University of Cologne, and Max-PlanckInstitute for Neurological Research, Cologne, Germany Margaret Fahnestock, PhD Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada Nanna B. Finnerup, MD Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark David J. Gladstone, MD, FRCPC, PhD Division of Neurology and Regional Stroke Centre, Sunnybrook Health Sciences Centre; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada

ix


x

CONTRIBUTING AUTHORS

Allan Gordon, MD, FRCPC Wasser Pain Management Centre, Mount Sinai Hospital; Department of Medicine, University of Toronto, Toronto, Ontario, Canada Alexander L. Green, MRCS Department of Neurological Surgery, Radcliffe Infirmary, Oxford, United Kingdom Clement Hamani, MD, PhD Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada Walter F. Haupt, MD Clinic for Neurology, University of Cologne, and Max-PlanckInstitute for Neurological Research, Cologne, Germany Wolf-Dieter Heiss, MD Clinic for Neurology, University of Cologne, and MaxPlanck-Institute for Neurological Research, Cologne, Germany James L. Henry, PhD Michael G. DeGroote Institute for Pain Research and Care, Health Sciences Center, and Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada Troels S. Jensen, MD, PhD Danish Pain Research Center and Department of Neurology, Aarhus University Hospital, Aarhus, Denmark Anthony K.P. Jones, MB BS Human Pain Research Group, Institute of Neuroscience, University of Manchester, Manchester, United Kingdom Henriette Klit, MD Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark Chitra Lalloo, McMaster University, Hamilton, Ontario, Canada Marc Levivier, MD, PhD Department of Neurosurgery, ERASME Hospital, University of Brussels, Brussels, Belgium Andres M. Lozano, MD, PhD, FRCSC Division of Neurosurgery and Toronto Western Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada Angela Mailis Gagnon, MD Comprehensive Pain Program, Toronto Western Hospital, University Health Network, and University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada Monica Marchese, PhD Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada Sarah L.F. Owen, BA(Hons) University Laboratory of Physiology, University of Oxford, Oxford, United Kingdom Akbar Panju, MB, ChB, FRCP(C), FRCP(Edin), FRCP(Glasg) Michael G. DeGroote Institute for Pain Research and Care, Health Sciences Center, McMaster University, Hamilton, Ontario, Canada Benoit Pirotte, MD Department of Neurosurgery, ERASME Hospital, University of Brussels, Brussels, Belgium


CONTRIBUTING AUTHORS

xi

Birgit Schumacher, MD Clinic for Neurology, University of Cologne, and MaxPlanck-Institute for Neurological Research, Cologne, Germany Barry J. Sessle, MDS, PhD, DSc(hc), FRSC, CAHS Faculty of Dentistry, Faculty of Medicine, and Centre for the Study of Pain, University of Toronto, Toronto, Ontario, Canada John F. Stein, DPhil, FRCP University Laboratory of Physiology, University of Oxford, Oxford, United Kingdom Alexander Thiel, MD Department of Neurology, SMBD Jewish General Hospital and Lady Davis Institute, McGill University, Montreal, Quebec, Canada; Clinic for Neurology, University of Cologne, and Max-Planck-Institute for Neurological Research, Cologne, Germany A.R.M. Upton, MA, MB, BChir, LRCP, MRCS, FRCPC, FRCPE, FRCPG Neurology Division, Department of Medicine, McMaster University, Hamilton, Ontario, Canada Philippe Voordecker, MD Department of Neurosurgery, ERASME Hospital, University of Brussels, Brussels, Belgium Alison Watson, BSc Human Pain Research Group, Institute of Neuroscience, University of Manchester, Manchester, United Kingdom David Wikler, MS Department of Neurosurgery, ERASME Hospital, University of Brussels, Brussels, Belgium Lutz Winhuisen, MD Clinic for Neurology, University of Cologne, and Max-PlanckInstitute for Neurological Research, Cologne, Germany Qi Wu, MD, MS Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada Kiran Yashpal, PhD Michael G. DeGroote Institute for Pain Research and Care, Health Sciences Center, McMaster University, Hamilton, Ontario, Canada


Preface Hippocrates described the sudden onset of dizziness and paralysis in some of his patients as apoplexia, from the verb apoplessein, meaning “to strike down.” The mysterious affliction may have seemed like being struck down at the whim of the gods. Although we now know that a stroke is caused by cerebral embolism, hemorrhage, or thrombosis, the central pain that can develop after a stroke remains a mystery. A paper published by Dejerine and Roussy in 1906 provided the first comprehensive description of “thalamic syndrome.” Unfortunately, the problems of what is currently referred to as “central poststroke pain” are as complex now as they were 100 years ago. However, with the advent of the amazing scientific tools available to us today, the hope for progress in understanding this syndrome has gained momentum. This volume is based on the 5th IASP Research Symposium, entitled “Central Neuropathic Pain: Centenary of Central Poststroke Pain,” held in Toronto, Ontario, Canada, in June 2006. The symposium brought together basic and clinical scientists, epidemiologists, and neurologists from around the world to learn from each other’s perspectives on the fundamentals of central neuropathic pain. The ultimate goal of the symposium was to develop consensus guidelines for the treatment of central poststroke pain. Contributing authors, each an expert in at least one aspect of stroke, pain, or central neuropathic pain, have sought to present current developments in the field while placing them into a broader perspective. The resulting volume represents current knowledge of the mechanisms of central poststroke pain, including the role of the thalamus. The latest therapeutic approaches are reviewed, and best practice guidelines are provided to guide the clinician through the complex maze of treatment options. This volume represents only one step toward the ultimate goal of relieving the excruciating pain suffered by some individuals who have experienced a stroke. One day this dream will become a reality. We are grateful for having had the opportunity to host the symposium and edit this volume. The enthusiastic participation of the contributing authors and their desire and determination to solve the puzzle of central poststroke pain have given patients a shining ray of hope. xiii

James L. Henry Akbar A. Panju Kiran Yashpal


Central Neuropathic Pain: Focus on Poststroke Pain, edited by James L. Henry, Akbar Panju, and Kiran Yashpal, IASP Press, Seattle, © 2007.

2 Brief Historical Aspects of Central Poststroke Pain and a Case History of a Patient Suffering from this Condition Akbar Panju Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada

The longer you look back, the farther you can look forward Sir Winston Churchill, 1874–1965 The first description of central pain was made by Greiff (1883), who described central pain in his report of a patient who, following cerebrovascular lesions including the thalamus, developed lasting pain described as “reissende Schmerzen” (tearing pains). Edinger (1891) presented arguments for the existence of central pain. By then it was known that sensory nerve pathways project to the thalamus, which was thought to play a critical role in central pain. In 1906, French neurologists Dejerine and Roussy described post mortem findings in three patients who had pain after stroke and correlated the clinical features with the pathological findings of lesions that included the “external nucleus of the thalamus (lateral and posterior portions especially).” The “thalamic syndrome” described by Dejerine and Roussy had the following features: mild hemiplegia without contractures; superficial hemianesthesia with impaired deep sensation; mild hemiataxia and astereognosis; choreoathetosis on the paralyzed side; and sharp, enduring, paroxysmal, often intolerable pain, on the hemiplegic side, that does not respond to any analgesic treatment. Ever since the description of the thalamic syndrome, thalamic pain has remained the best-known form of central pain. Although interest in central pain focused mostly on thalamic pain for many years, multiple subsequent investigators introduced the idea that lesions in other areas of the central nervous system could cause pain. It has now been demonstrated beyond doubt by multiple investigators that lesions above the thalamus, in the brainstem, and in the spinal cord can cause central pain. The causes of central pain are highlighted in Table I. 




A. panju Table I Causes of central pain Vascular lesions in the brain and spinal cord Infarction Hemorrhage Vascular malformation Multiple sclerosis Traumatic spinal cord injury Cordotomy Traumatic brain injury Syringomyelia and syringobulbia Tumors Abscesses Inflammatory diseases other than multiple sclerosis Myelitis causes by viruses or syphilis Epilepsy Parkinson’s disease

Since similar pain can arise after strokes that cause lesions not just in the thalamus but in any part of the somatosensory pathway, the term “”thalamic pain” has now been replaced by “central poststroke pain” to describe the central neuropathic pain that occurs in patients affected by stroke. Head and Holmes (1911) and Riddoch (1938) offer many fascinating, detailed descriptions of symptoms and signs of central pain. Many of these accounts show that the character of pain may vary considerably from patient to patient and that it can be excruciating. Authors vividly describe the pain as a crushed feeling, as a scalding sensation, as a cold, stinging feeling, as if boiling water were poured down the arm, as if the leg were bursting, like something crawling under the skin, like pain pumping up and down the side, as if Henry\Tables\Panju the painTable II ful region were covered with ulcers, like pulling a dressing from a wound, as if a log were hanging from the shoulder, or like a wheel running over the arm. Table II describes the qualities of pain reported by patients with central pain. Table II Qualities of pain reported by patients with central pain Burning* Aching* Lancinating* Pricking* Lacerating* Pressing* Shooting

Squeezing Throbbing Cutting Crushing Splitting Stinging Stabbing

Cramping Smarting Pulling Sore Icy feeling

*Asterisks indicate the most common qualities.


Central Neuropathic Pain: Focus on Poststroke Pain, edited by James L. Henry, Akbar Panju, and Kiran Yashpal, IASP Press, Seattle, © 2007.

4 Clinical Characteristics of Central Poststroke Pain Henriette Klit,a Nanna Brix Finnerup,a and Troels S. Jensena,b Danish Pain Research Center and bDepartment of Neurology, Aarhus University Hospital, Aarhus, Denmark

a

Definition and Characteristics of Central Pain

Central pain is defined by IASP as “pain initiated or caused by a primary lesion or dysfunction in the central nervous system.” It is a neuropathic type of pain that is not due to factors such as peripheral neurogenic, nociceptive, or psychogenic pain. Central pain can be caused by lesions in the spinal cord or in the brain itself. There are multiple etiologies for central pain, including stroke, subarachnoid hemorrhage, traumatic injury to the spinal cord or brain, myelitis, syringomyelia and syringobulbia, multiple sclerosis, cordotomy, dorsal root end zone lesions, and epilepsy. Central pain is characterized by spontaneous and evoked pain. It can be described as either superficial, deep, or both. Often, a loss of sensation is found on examination, often with paradoxical hyperalgesia in the same area. Many cases involve both thermal hyperalgesia and loss of sensitivity to heat. history and definition of Central PostStroke Pain

Central poststroke pain (CPSP) is the most common cause of central pain, accounting for approximately 90% of all central pain related to lesions in the brain (Tasker et al. 1991). It was previously thought to occur only in patients with thalamic lesions and was therefore known as the thalamic syndrome (Boivie and Leijon 1991). One of the first descriptions of this syndrome is that of Dejerine and Roussy (1906), who described patients with thalamic lesions, slight hemiplegia, abnormal superficial and deep sensitivity, hemiataxia and 27


MECHANISMS OF THALAMIC PAIN 85

bilateral, rather than unilateral, leg pain. The latter observation in particular accords with the possibility that more than one cause exists for central neuropathic pain. However, Beric also observed that central pain is comparatively rare after anatomically complete spinal transections; this observation is consistent with the idea that an imbalance between ascending spinothalamocortical activity on the two sides may be particularly important (see below). Plastic reorganization in the lateral thalamus of some chronic pain patients is suggested by observations that microstimulation in the region of somatosensory thalamus that was deafferented by a lesion of ascending lemniscal fibers can elicit reports of phantom pain or central pain (Lenz and Dougherty 1997). This phenomenon contrasts starkly with the fact that such stimulation in nonpain patients almost never causes pain, suggesting that maladaptive reorganization may have occurred. However, the stimulation-produced pain reported in such cases was almost always referred to a topographically inappropriate body location, which is consistent with the simpler explanation that such stimulation excited thalamocortical passing fibers from a more posterior site (i.e., VMpo). THE THERMOSENSORY DISINHIBITION HYPOTHESIS OF CENTRAL PAIN

I have described this idea in several prior articles (Craig 1998, 1999, 2000, 2002). In the following text, I summarize the hypothesis and present corroborative findings on the role of the medial thalamus. This hypothesis proposes that central pain is a thermoregulatory disorder, in accordance with the view that pain is a distress signal produced and modulated by homeostatic processing, that is, a homeostatic emotion (Craig 2003b). Specifically, this idea proposes that a lesion that interferes with the output of the lamina I spinothalamocortical terminus in the primate thermosensory (interoceptive) cortical area in the dorsal posterior insula disinhibits a limbic network involving brainstem homeostatic sites (the parabrachial nucleus, periaqueductal gray matter), medial thalamus (MDvc), and anterior cingulate cortex (ACC).The disinhibition of this limbic network generates strong negative motivational affect (unpleasantness, discomfort, and burning pain) representing thermoregulatory motivation. This concrete anatomical hypothesis is remarkably similar in outline to the original disinhibition proposal by Head and Holmes (1911), although it suggests that the key interruption is the loss of the discriminative thermosensory representation, rather than of the discriminative pain representation.


86

A.D. CRAIG

Crucial characteristics

The thermosensory disinhibition hypothesis incorporates several clinical characteristics of central pain (see chapters by Jensen and Boivie in this volume): 1) Virtually all central pain patients have a thermosensory deficit in the body region where the ongoing pain is perceived. This is a cardinal feature. Some have only elevated warm and cool thresholds, but most have dense regional thermanesthesia. Importantly, the ongoing pain is referred to the same region of the body where the thermosensory dysfunction is focused, clearly suggesting a causal relationship. Similar symptomatology has been reported by many authors for the so-called “burning mouth syndrome,” suggesting that it can be viewed as an orofacial version of the central pain syndrome. 2) The anatomical locations of lesions found in central pain patients nearly always coincide with the ascending lamina I spinothalamocortical pathway to the dorsal posterior insula (i.e., lateral spinothalamic tract, ventrolateral medulla, dorsolateral brainstem, posterolateral thalamus, posterior internal capsule, posterior insula). This observation can explain the clinical thermosensory deficits, because this ascending pathway is the unique substrate for discriminative thermal sensation in humans (Craig 2000, 2003a; Maihofner et al. 2002). In fact, loss of the cortical terminus of this pathway, the thermosensory cortex within the dorsal posterior insula, is critical for the occurrence of central pain after supra-tentorial stroke (Schmahmann and Liefer 1992). Many central pain patients also have clinical deficits in evoked pain sensation, which is consistent with the view that the lamina I spinothalamocortical projection to the dorsal posterior insula is crucial for both discriminative thermal sensation and discriminative pain sensation (Craig 2003a). (A recent report in the journal Pain claimed that central pain occurred in a patient with a thalamic lesion that did not damage the VMpo; however, the authors reported that the patient had a dense thermal hypoesthesia, and so the VMpo must have been involved, because it is the unique thalamic substrate for thermal sensation; see Montes et al. 2005). 3) At least half of central pain patients experience the onset of the ongoing pain immediately following the precipitating incident. This observation is consistent only with the mechanism of disinhibition. Other patients experience pain after a delay of weeks to months, and viewing central pain as a thermoregulatory dysfunction implies that delayed onset could represent maladaptive homeostatic acclimatization (see below). 4) Most central pain patients describe the ongoing pain as “burning,” like cold pain. This description is consistent with the view that central pain represents a thermoregulatory distress signal. Many central pain patients report cold allodynia, which is also consistent with thermoregulatory dysfunction. Others


122

K.L. CASEY

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Fig. 4. Borderline hypoperfusion bilaterally in the medial and intralaminar thalamus (blue ovals) of Patient 3 with painless peripheral denervation of the left arm. The resting perfusion of the patient’s right thalamus (arrow, upper right PET image) appears low, but was within the Z score range of ¹ 2 of normal subjects. This patient did not have a hyperresponsive thalamus during noxious heat stimulation.

SIGNIFICANCE OF THE CLINICAL FINDINGS

Two of the three CPSP patients described above have increased thalamic excitability in the presence of resting thalamic hypoperfusion. Assessment of this condition requires an estimate of the resting perfusion level and of the change in perfusion during stimulation, which requires an imaging procedure such as H215O PET or possibly arterial spin labeling. These patients also show that this condition may follow ischemic damage to a major afferent path to the thalamus but remote from it at the spinal level (the STT in patient 1), or it may


AN ANIMAL MODEL OF CPSP

177

(no movement) is observed, a filament exerting greater force is applied, and if a positive response (paw withdrawal from the platform) is observed, a filament of lesser force is used next. Each filament is applied three times, at 3-second intervals. A 50% response threshold is calculated according to the response pattern observed. The maximum score possible is 15 g, and the minimum is 0.25 g. Thus, control rats tend to exhibit withdrawal thresholds at 15 g. Neuropathic rats exhibit withdrawal thresholds around 2 g. Other animal models of chronic pain show unique withdrawal thresholds. Thus, any drug that has an analgesic effect will act to raise this threshold toward or to 15 g. SIMILARITIES BETWEEN THE ANIMAL MODEL AND HUMAN SUFFERING FROM CPSP

To date our focus has been on whether there are any signs of ongoing or evoked hypersensitivity in this hemorrhagic stroke model. Several signs have indicated hyperexcitability to innocuous and noxious stimuli, the animal equivalents of allodynia and hyperalgesia in humans. These conditions are both characteristic of neuropathic pain, including CPSP. Given that lesions were placed at different sites in and around the thalamus, not all animals exhibited signs of hypersensitivity. Symptoms observed in the affected animals included spontaneous elevation of one hindpaw, a stiff tail, vocalization on handling, and withdrawal of the limb to touch, pressure, and gentle pinching. Signs that were not observed in any animals were hunched-back posture, matted hairs on the back, and behaviors such as backing into a corner. These are signs of unacceptable levels of ongoing pain. The lack of these signs indicates that the model is not so severe that one is unlikely to see any beneficial effect of any therapeutic drug. Overall, the observations to date would indicate that this is a suitable model in which to test the effectiveness of a novel candidate drug for the treatment of central neuropathic pain. Are we modeling human central poststroke pain?

Human CPSP can be due to a lesion anywhere in the spinothalamic tract including the spinal cord and cortex and everything in between. Therefore, there is no single entity that is central poststroke pain in humans, and thus a single animal model cannot model all kinds of CPSP. We chose to model the most common type of CPSP in humans, which is pain due to a stroke-induced lesion in the sensory thalamus. This lesion in the sensory thalamus can be induced by either ischemic or hemorrhagic stroke.


CORTICAL MODEL OF ALLODYNIA

203

Some Reflections and Speculations on the Management of Poststroke Pain

The extent to which there are shared pharmacological mechanisms between fibromyalgia and central pain may not be resolved for some years. Meanwhile, many thousands of patients will have suffered unpleasant pain for varying durations after a stroke. There are several significant barriers to the effective management of poststroke pain. The first is a general lack of awareness amongst physicians and patients. This lack of awareness extends to some of the specialists within the stroke community. Communication about this phenomenon may therefore be the first priority. To those of us who treat poststroke pain regularly, it is clear that the majority of patients can be returned to a reasonable quality of life over a period of time by the logical use of pharmacological, psychological, physical, and on occasion physiological (brain stimulation) interventions. In those with poststroke shoulder pain, the outlook is reasonably good; 70% of patients will have resolution of their pain within 6 months with early intervention with shoulder injection of steroids and local anesthetic or low-dose amitriptyline for depression and sleep disturbance where appropriate. However, in some patients, particularly those with classical central deafferentation pain, substantial improvement in their pain may take 2–3 years or longer. The key to success is the engagement of a physician or health care specialist who is prepared to facilitate treatment by a multidisciplinary team of therapists with tempered optimism and kindness. For clinicians who are unfamiliar with poststroke pain, guidelines will be key to gaining confidence in managing this condition (see the chapter by Gordon in this volume). It is also important to constantly reevaluate goals with each patient. Some patients may have surprising beliefs about their treatments. For instance, the belief that the goal of opioid analgesia was to completely ablate the pain, and that progress could only be made in the complete absence of pain, led one of our patients to escalate his dose to levels that caused respiratory depression. Other patients may believe that a worsening of the pain is a sign that they may be about to have another stroke. Such beliefs and expectations can make a substantial difference to a patient’s response to therapy and acceptance of the symptoms and may affect the timeframe in which therapeutic interventions can most usefully be used. The sequential or simultaneous use of pharmacological, cognitive, and physical rehabilitation approaches is necessary because patients may progress very slowly. Optimism and encouragement from the therapist are important in maintaining progress, however slow. Over the last 7 years, Hope Hospital in Manchester has operated a multidisciplinary poststroke pain service based on these principles. When we started this service, we had a very large number of patients with severe poststroke pain.



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