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The Phenomenon of

Pain by Serge Marchand

The Phenomenon of Pain

Mission Statement of IASP Press

The International Association for the Study of Pain (IASP) brings together scientists, clinicians, health care providers, and policy makers to stimulate and support the study of pain and to translate that knowledge into improved pain relief worldwide. IASP Press publishes timely, high-quality, and reasonably priced books relating to pain research and treatment.

The Phenomenon of Pain

Serge Marchand, PhD Neurosurgery Division, Department of Surgery Faculty of Medicine and Health Sciences, Sherbrooke University Étienne-Le-Bel Clinical Research Center, Sherbrooke University Hospital Sherbrooke, Quebec, Canada




© 2012 IASP Press International Association for the Study of Pain


Copyright © 2009 Chenelière Éducation inc. This translation of Le phenomène de la douleur, 2nd edition, is published by arrangement with Chenelière Éducation inc. 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 The Phenomenon of 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. Translated from the Le phenomène de la douleur, 2nd edition, by Serge Marchand PhD, with the support of the University of Sherbrooke Faculty of Medicine, le centre hospitalier universitaire de Sherbrooke, and le centre de recherché Clinique Étienne Le Bel.

Library of Congress Cataloging-in-Publication Data Available from the publisher.

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


Printed in the United States of America


Introduction 1. What Is Pain?


2. Concepts of Neurophysiology


3. Neurophysiology of Pain


4. Theories of Pain


5. Measuring Pain


6. Pharmacological and Surgical Approaches to Pain Control


7. Nonpharmacological Pain Treatments


8. Pain and Age


9. Differences Between Men and Women in Pain: More Than a Matter of Perception


10. Pain: From Innate to Acquired


11. Pain Clinics









Serge Marchand, PhD, is a professor in the Neurosurgery Division, Department of Surgery, Faculty of Medicine and Health Sciences, Sherbrooke University, and Director of the Étienne-Le Bel Clinical Research Center of Sherbrooke University Hospital. He received his doctorate in neuroscience from the University of Montreal in 1992 and then completed his postdoctoral training in neuroanatomy at the University of California in San Francisco in 1994. He is a world-renowned expert in the field of pain mechanisms and treatment. His research is characterized by a close link between fundamental and clinical projects on the neurophysiological mechanisms implicated in the development and persistence of chronic pain.

INTRODUCTION Pain is a universal experience from birth until the end of life. Generally, it is mild and inconsequential, as is the case when we feel a tingling in the legs after keeping them in the same position too long or when we accidentally hit our fingers against the edge of the table. Nevertheless, all too often, pain is intolerable and requires treatment, or else it persists beyond the healing of the injury and becomes chronic, reducing activities and sometimes making life unbearable. More than 80% of people seeking medical care have pain as the reason for their consultation. In addition, we are not all equal in the face of pain. Pain is sexist: women suffer more than men. Pain changes with age: elderly people are more likely to suffer from chronic pain than younger people. Its treatment is complex and requires consideration of the type of pain that we are confronted with and the characteristics of the person suffering from it. Can we identify the cause and treat the diseased organ? Is it the result of sensitization of the central nervous system from a cause that cannot be identified? Is the pain at an acute stage, or is it chronic? Is the patient a child, a young adult, an elderly person, a man or a woman? Is the patient depressed? All this information and much more is essential if we are to choose the treatment that has the greatest chance of success. The clinician must constantly deal with the reality of human suffering and its complexity. This daily contact with pain is often difficult for caregivers, and the inability to understand and relieve it causes them significant emotional stress. In terms of basic and clinical research, pain has been a growing concern in recent decades. The rapid evolution of knowledge has helped us to better understand the pain phenomenon, while highlighting the complexity of its neurophysiological and psychological mechanisms. Attitudes and ways of treating pain are also changing. We now know that pain is not only the result of pathology, but must often be treated as a problem in itself. Sometimes the patient has severe pain for months, or even years, without anyone being able to determine its cause or physiological basis. Not so long ago, we would have simply denied the existence of this suffering. Today, we have invented medical terms for such cases—occult pain, or idiopathic pain—which mean that we do not know the exact cause of pain. While it may seem simplistic, such a diagnosis at least recognizes that pain can exist even if we cannot determine its origin. Unfortunately, this openness is not shared by all clinicians, and the label of pain of psychological origin, or vii

somatization, too often suggests that the pain is “not real,� a diagnosis that is given for pain whose physiological origin is not clear. The prognosis indicates that medicine can do nothing for this patient. In this book, we discuss not only the physiological and psychological factors that are necessary for better comprehension of the development of pain, but also those involved in its persistence. These factors are discussed in relation to pharmacological and nonpharmacological treatments in an attempt to create a link between the mechanisms of pain and the mechanisms of the therapeutic approaches. Understanding this link will allow the clinician to adapt the treatment depending on the type of pain the patient is dealing with. The ultimate goal of this book is to promote better understanding of pain in order to maximize its relief and to prevent acute pain from becoming chronic.



Fig. 3.

Circular pain model.

threshold must be reached, and second, numerous mechanisms can block these afferents. (See component 1 of Fig. 3.) Distraction can block the perception of pain. A boy is playing outdoors and is preoccupied with his game. He falls and scrapes himself mildly. Since he is busy with his game, he does not really feel the pain, even if the injury has caused an actual activation of the nerve fibers responsible for nociception. On the clinical level, therefore, the recording of nociceptive information is not enough to measure pain. Stimulations of the same intensity can produce withdrawal reflexes of the same amplitude, but they may or may not cause pain, depending on the context. Absence of pain indicators in a patient is not evidence of absence of a serious pathology. In the event of a very stressful situation, a car accident for example, we cannot rely only on the verbal report of the accident victim, who may show significant trauma without necessarily expressing pain. What is Pain?


equilibrium and behaviors. The hypothalamus controls the master gland of the body, the pituitary gland (hypophysis), which is situated just below it. These two structures together play a predominant role in maintaining homeostasis by regulating the endocrine system. In particular, they control body temperature, appetite, fluid balance, and sexual activity. The hypothalamic-pituitaryadrenal axis is the origin of our stress responses through the release by the hypothalamus of a cascade of neurohormones, including corticotropin-releasing hormone (CRH), which then activates the secretion of adrenocorticotropic hormone (ACTH). In turn, this hormone ensures the release of cortisol by the adrenal glands. These functions are particularly important for understanding the link between stress and pain.

The Telencephalon The telencephalon constitutes the major part of the brain. It is made up of the cerebral hemispheres and the superior nuclei. The interhemispheric fissure divides it into two hemispheres, including all four lobes visible from the exterior and a fifth part, the insular lobe, located beneath them (see Fig. 21). Fig. 21. The telencephalon. Adapted from [1], p. 209.

Concepts of Neurophysiology


inhibition of CNS nociceptive afferents (see Fig. 14). These are: (1) spinal mechanisms that produce localized effects; (2) descending inhibitory controls that produce diffuse effects; and (3) mechanisms of the higher centers that, depending on the circumstances, may be diffuse or local in nature.

Spinal Mechanisms Since the famous gate theory of Melzack and Wall [67], the modulation of nociceptive information when it enters the spinal cord has been well documented. In 1965, Melzack and Wall proposed that the selective stimulation of large-caliber afferents—Aβ fibers—recruits inhibitory interneurons into the substantia gelatinosa of the dorsal horns of the spinal cord. According to their theory, represented in a simplified way in Fig. 14, level 1, the selective stimulation of large afferent Aβ fibers blocks the small nociceptive Aδ and C fibers in the substantia gelatinosa (lamina II) of the dorsal horn of the spinal cord. An inhibitory interneuron, recruited by the large fibers responsible for nonnociceptive afferents (Aβ fibers) and inhibited by the small nociceptive fibers (Aδ and C fibers), modulates pain in the spinal cord. The medullar activity of excitatory and inhibitory messages is then integrated into the targeted projection Fig. 14. Endogenous inhibitory mechanisms.

Neurophysiology of Pain


Fig. 1. Hierarchy of analgesic prescriptions according to the World Health Organization.

peripheral analgesics (e.g., aspirin), level II for low-potency central analgesics (e.g., codeine), and level III for high-potency central analgesics (e.g., morphine). Dosage also presents a major challenge for the caregiver. The ideal dose should produce analgesia as fully as possible while avoiding adverse effects (see Fig. 2). It is important to remember that a transition from one level to another in the therapeutic scale should only be done if the medication at the first level has been used properly. The apparent inefficacy of a medication may be: (1) from inadequate dosage; (2) from too long an interval between doses of medication; (3) from forgetting to combine it with a coanalgesic when appropriate. Fig. 2.

Analgesic dosage scale.

Pharmacological and Surgical Approaches


Recommendations for the Clinical Use of TENS The clinical success of TENS depends on its proper use. Correct positioning of the electrodes and suitable stimulation parameters are essential for a good effect (see Figs. 2 and 3). Furthermore, it is important to remember that TENS produces mild analgesia, generally reducing pain by less than 50%. Nevertheless, in some chronic conditions, even a small reduction in pain can make all the difference. Just think of analgesia produced by aspirin: you would not recommend it to block pain during dental surgery, but you would offer it for a headache. The same logic applies to TENS. Fig. 2.

TENS and low back pain.

Here are the main parameters of stimulation that need to be checked: the frequency, intensity, duration, wavelength, and location of the electrodes. It is important to remember that only the patient is able to judge whether each parameter is properly adjusted to produce maximal analgesia. Good patientcaregiver collaboration is therefore essential. Frequency The frequency is generally set between 50 and 100 Hz. One procedure that can be used is to start at a low frequency and to ask the patient when the Fig. 3.

Electrical wave.

Nonpharmacological Pain Treatments


Studies maintain that clinical use of acupuncture relieves chronic pain associated with dysmenorrhea [152], fibromyalgia [41], joint pain [48], and some types of headache [103]. Much work remains to be done to elucidate the neurophysiological mechanisms of acupuncture and the physiological substrate of acupuncture points. However, even if we do not know all of its foundations, this technique can provide relief in some patients.

Stimulation of Trigger Points Another important phenomenon in peripheral nociceptive stimulation is that of the trigger points. These points are extremely sensitive areas that cause intense pain when they are stimulated (see Fig. 7). Trigger points are usually located close to the painful area, but sometimes they are at a considerable distance from it. They are generally associated with a condition such as back pain or tension headache. Although less numerous, trigger points also exist in healthy subjects. Stimulation of these areas causes pain or exacerbates existing pain. One of the treatments associated with trigger points is an injection of a local anesthetic. This approach is widely used in pain clinics for the relief of chronic pain such as low back pain. One explanation for the neurophysiological functioning of the trigger points is based on the convergence of visceral and somatic fibers. Cells of lamina V receive converging fibers from the skin and viscera. Visceral pain therefore Fig. 7.


Trigger points.

The Phenomenon of Pain

IT’S A FACT: WOMEN HAVE MORE PAIN THAN MEN Chronic Painful Pathologies Several epidemiological studies report a higher prevalence of chronic painful diseases in women compared to men. Women are also more likely to develop chronic pain conditions such as headaches, rheumatoid arthritis, fibromyalgia, abdominal pain (e.g., irritable bowel syndrome), and musculoskeletal pain [13,14,27,116,134].

The Perception of Pain The literature also shows that there are significant differences between men and women in regard to the perception of pain. In addition to the fact that women have more painful problems, most studies report that women perceive clinical pain more intensely and for a longer period of time than men [38]. Animal studies also report this type of observation, especially in terms of visceral pain [9]. A multitude of evidence from studies of experimental pain confirms the differences between men and women in terms of pain perception. Fillingim and Maixner [40] report that 66% of the 34 studies they reviewed suggest that women experience more pain than men. Subsequently, Berkley [13] was able to support this observation by adding that women perceive more pain than men from the same stimulus, although the differences observed were relatively minor and inconsistent. A few years later, in a meta-analysis that included 22 of the 34 studies used by Fillingim and Maixner [40], Riley and his collaborators [110] opted for a statistical approach (effect size) rather than a count, and thus determined a significant effect, demonstrating that women have a lower pain threshold and tolerance to experimental pain than men, whether the stimulus was mechanical, thermal, or electrical. However, it is known that the size of these differences may be influenced by several interacting factors that contribute to the variability in the response to pain. These variables influence the magnitude of the differences between men and women and lead to some variability in the results [81]. Fig. 1, adapted from Dao and LeResche [27], shows all of these factors. These various items illustrate the complexity of the phenomenon. Thus, the variability of results between studies may be explained by several factors, such as the type of stimulus: thermal, mechanical, electrical, or ischemic [62]. Moreover, the temporal characteristics of the stimulus, that is, whether it is phasic or tonic [44,103], as well as the spatial characteristics related to the surface stimulated [118,119], can affect the response to pain. Responses can also vary depending on the type of measure, such as pain 272

The Phenomenon of Pain

Environmental Factors External stress factors and a history of pain [52] or abuse [34] also appear to be good predictors of the development of chronic pain. Education also plays a considerable role in the predisposition to chronic pain [11]. For example, a child who sees a parent pay attention to him when he hurts himself is more likely to develop pain sensitization [16]. Interestingly, it has recently been shown that children who were born prematurely and received painful clinical procedures are more sensitive to pain throughout their lives [6,24,25]. The increased sensitivity in these children can be explained by a deficit in pain inhibition mechanisms. Recently, a study has also reported that children born prematurely who were exposed to several nociceptive stimuli during their medical care showed a deficit in DNIC when they were assessed later in childhood [24].

Psychological Factors Finally, psychological factors such as anxiety, depression, or catastrophic thinking are also important predictors of chronicity of pain [1,13,22,41]. Pain is a perception, and its interpretation is influenced by past experiences and emotions [43]. It is important to remember that psychological factors not only predict reactions to the painful experience or the ability to cope with pain, but they also have an impact on the evolution of symptoms of chronic pain. Pain treatment should, therefore, always take into consideration that psychological factors play an important role in the development of chronic pain [18].

THE ROLE OF ACQUIRED FACTORS IN CHRONIC PAIN Pain According to Race, Culture, and Ethnicity Many studies have focused on the relationship that exists between race, culture, and ethnic groups, on the one hand, and the experience of pain, on the other hand, but it is difficult to draw final conclusions. Two reasons explain this difficulty. First of all, to compare races, cultures, or ethnic groups, enormous human, material, and financial resources are often necessary and, as a result, many research teams are unable to carry out studies in this direction. However, it is the lack of adequate measurement tools that represents the main limiting factor. Indeed, as the pain experience is a perception, the contribution of the suffering person is essential to the measurement of pain, both in regard to its intensity and its unpleasantness. Consequently, it is very difficult to compare the pain experience of two people, each using their own language and using terms that often do not have an equivalent in the language of the other. Fortunately, the visual analogue scale (VAS) as well as Pain: From Innate to Acquired


The Phenomenon of Pain describes the physiological and psychological mechanisms involved in the development and persistence of pain. Serge Marchand provides practical details on treatment methods, outlining pharmacological as well as nonpharmacological options, and presents a case for an interdisciplinary approach. This adaptation of the original French version helps the reader understand the various factors surrounding the complex phenomenon of pain. “This book is a fascinating book on pain and a must for any pain professional. It is important for any person who would like to understand the phenomenon of pain and how it can become intolerable and persist beyond the healing of the injury to making life unbearable for patients, their families and peers. A well-written, easy-to-read, and up-to-date book, The Phenomenon of Pain enables the reader to understand the complexity of what pain represents for a patient. The author shows how physiological and psychological factors closely interact in the perception of the pain and in its persistence. The management of pain must be seen through a biopsychosocial approach that includes both pharmacological and nonpharmacological treatments. In promoting better understanding of pain in order to maximize its relief and prevent acute pain from becoming chronic, Marchand has certainly succeeded.” Chantal Wood, MD, Robert Debré Hospital, Paris, France Serge Marchand. PhD, is a Professor of Medicine at the University of Sherbrooke, Quebec, Canada, and the Director of the Étienne-Le Bel Clinical Research Center at Sherbrooke University Hospital. He is a recipient of the Édouard-Montpetit Medal for his research on pain treatment in Quebec, Canada, and is a member of the Canadian and American Pain Societies. The Phenomenon of Pain is a updated translation of Le phenomène de la douleur (Quebec, Chenelière Éducation, 2009). ISBN 978-0-931092-91-6


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