Functional Pain Syndromes: Presentation and Pathophysiology

Q: Is there any overlap among the functional pain syndromes?
A: Specialists tend to develop symptom-based criteria for each syndrome without considering the frequent overlap of these syndromes with one another and with psychiatric syndromes, such as anxiety, depression, and somatization. Only recently have clinicians and investigators begun to focus on the shared features of these syndromes. This book brings together experts from the fields of pain medicine, gastroenterology, psychiatry, physiology, genetics, and neuroscience who review the growing evidence that these disorders have substantial comorbidity with each other.

Q: Are these disorders considered “psychosomatic” in origin?
A: The term psychosomatic has traditionally been associated with a conceptualization of physical disease as a manifestation of psychological processes and conflicts. Thus, this term does not reflect the current view that these syndromes are based on an altered bidirectional interaction between the nervous system and the body. Central pain amplification and altered autonomic nervous system activity are two of the mechanisms most commonly implicated in generating symptoms. Nevertheless, experts have come to recognize psychological factors—chronic stress and symptom-related worry in particular—as important factors in symptom onset and severity.

Q: Why are functional disorders more prevalent in women?
A: Although it could be said that women in general are more likely to consult a health care provider when they have symptoms of illness, there is good evidence that these syndromes really are more common in women. Preliminary evidence suggests that sex-related differences in emotional arousal circuits and in endogenous pain modulation systems may play a role in the greater vulnerability of women. In addition, we have an incomplete understanding of the role of sex hormones.

Q: Do these disorders have any pathophysiological aspects in common?
A: The traditional, subspecialty-focused view of these disorders has emphasized the differences and ignored the shared features. This book represents a new perspective that has begun to emerge in the past five years. The occurrence of different functional disorders in the same patient (either at the same time or at another point during his or her lifetime), the comorbidity with certain psychiatric disorders, shared risk factors (early life trauma and gene polymorphisms), the sensitivity of symptoms to stress, and a good response to centrally targeted therapies (cognitive-behavioral therapy or low-dose tricyclic antidepressants) all point toward shared pathophysiological mechanisms.

Q: How do anxiety and depression relate to functional pain disorders?
A: Numerous epidemiological studies have demonstrated a high prevalence of psychiatric diagnoses (most commonly, anxiety and depression) in patients with these syndromes. Increased levels of depression, anxiety, and somatization (a high number of somatic complaints) are typical in most patients. Certain syndromes, such as IBS, tend to show comorbidity with anxiety, while others, such as FM, show a greater comorbidity with depression.

Q: Is there any evidence of a genetic predisposition to functional pain disorders?
A: Considerable evidence from twin studies, and more recently from studies of gene polymorphisms, indicates a genetic predisposition to develop these syndromes. Some of the best data come from prospective studies of the development of TMJD. Several obstacles stand in the way of our understanding of the role of heritability in functional disorders. First, these syndromes are likely to be polygenic disorders, where the contribution of each gene to the clinical phenotype may be less than 5%. Second, studies have been limited by the subspecialty-based definitions of different syndromes. A shared genetic predisposition for all these syndromes may manifest as IBS in one family member and as FM or TMJD in another, and this variable manifestation may be due to different environmental factors. Thus, the role of genetic factors and heritability may be significantly higher than is currently suggested.

Q: Does the book provide any new insights on post-traumatic stress disorder?
A: There is considerable comorbidity of many of the functional pain disorders with PTSD. Brain-imaging studies of patients with PTSD and functional pain disorders have demonstrated certain shared abnormalities in brain circuits, including a reduced ability to activate corticolimbic inhibition pathways. There may also be shared genetic and early-life vulnerability factors in PTSD and functional pain syndromes. The book explores these issues in the chapter on combat-related psychiatric syndromes.

Q: Does the book include treatment recommendations?
A: Most of the chapters on individual syndromes contain information about current therapies. In addition, specific chapters discuss the details of pharmacological, cognitive behavioral, and complementary and alternative therapies.

Q: Is there any overlap among the treatment options for these disorders?
A: There is considerable overlap among treatment options, particularly with centrally targeted therapies. Anxiolytics, low-dose tricyclic antidepressants, selective serotonin reuptake inhibitors, nonselective reuptake inhibitors, and nonpharmacological approaches (such as cognitive-behavioral therapy) all show benefit in subgroups of patients in different diagnostic categories.

Q: Are nonpharmacological approaches effective?
A: The best evidence for the effectiveness of such therapies comes from controlled trials into cognitive-behavioral therapy and hypnosis. An emerging view is that different subgroups of patients may benefit the most from pharmacological or nonpharmacological therapies (including cognitive-behavioral and complementary medicine approaches). A combination of these approaches may be synergistic.

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Contributing Authors
Foreword
Preface

Part I: Somatic Pain Syndromes

1. Fibromyalgia
   Daniel J. Clauw and David A. Williams
2. Chronic Back Pain
   James P. Robinson and A. Vania Apkarian
3. Temporomandibular Joint Disorders
   William Maixner
4. Vulvodynia
   Caroline F. Pukall and Yitzchak M. Binik

Part II: Visceral Pain Syndromes

5. Irritable Bowel Syndrome and Related Functional Disorders
   Lin Chang and Douglas A. Drossman
6. Sensitive Heart: A Chronic Cardiac Pain Syndrome
   Stuart D. Rosen and Paolo G. Camici
7. Painful Bladder Syndrome/Interstitial Cystitis
   Lori Birder and Christopher Chapple

Part III: Common Comorbid Syndromes in Relation to Pain

8. Combat-Related Psychiatric Syndromes
   J. Douglas Bremner
9. Anxiety in Functional Pain Disorders
   Bruce D. Naliboff and Jamie L. Rhudy
10. Chronic Pain and Depression
    Alan F. Schatzberg
11. Somatization and Pain Syndromes
    Francis Creed
12. Chronic Fatigue Syndrome
    Gudrun Lange and Benjamin H. Natelson

Part IV: Neurobiological Mechanisms Contributing to Symptoms

13. Autonomic Nervous System Dysfunction
    Wilfrid Jänig
14. HPA Axis and Sympathetic Influences on Pain and Fatigue
    Kathleen C. Light and Charles J. Vierck
15. Central Neuroglial Interactions in the Pathophysiology of Neuropathic Pain
    Ji Zhang and Yves De Koninck
16. Gut Microbiota and Abnormal Mucosal Neuroendocrine Immune Activation
    Robin Spiller and Fergus Shanahan
17. Visceral Hypersensitivity
    Fernando Cervero and G.F. Gebhart
18. Brain Correlates of Psychological Amplification of Pain
    Jürgen Lorenz and Irene Tracey

Part V: Environment-Gene Interactions and Chronic Pain

19. The Genetics of Pain
    Jeanette Papp and Eric Sobel
20. Early Life Trauma and Chronic Pain
    Elie D. Al-Chaer and Shelley A. Weaver
21. Genetically Driven Interactions in the Brain: Lessons from Depression
    Lukas Pezawas and Andreas Meyer-Lindenberg

Part VI: Treatment Strategies

22. Pharmacotherapy for Functional Somatic Conditions
    R. Bruce Lydiard
23. Cognitive-Behavioral Treatment of Functional Pain Disorders
    Jeffrey M. Lackner and Lance M. McCracken
24. Complementary Medicine and the Central Mediation of Functional Pain Disorders
    Ginger Polich, Jian Kong, Vitaly Napadow, and Randy Gollub

Part VII: Synthesis

25. Synthesis
    Emeran A. Mayer and M. Catherine Bushnell

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"Written by a panel of experienced medical professionals and edited by noted pain experts Emeran A. Mayer and M. Catherine Bushnell, Functional Pain Syndromes: Presentation and Pathophysiology offers in-depth information about the causes of functional pain syndromes, their manifestation, and potential treatment options. The pain syndromes examined include irritable bowel syndrome (IBS), fibromyalgia, functional dyspepsia, interstitial cystitis, and chronic cardiac pain. The authors focus on the growing body of evidence demonstrating that these pain-related disorders frequently co-exist in the same patient. This book is especially helpful because it explains how these syndromes compare to each other, detailing similarities and differences, and their correlation to anxiety, depression, post-traumatic stress disorder, and chronic fatigue syndrome. The authors explain a wide range of treatment options from cognitive behavioural therapy to antidepressants and other pharmaceuticals. This 580-page book contains a plethora of relevant information about pain syndromes, especially useful for medical professionals who treat individuals with IBS. A full chapter of information is dedicated to this disorder, including the co-morbidity between IBS and other functional pain syndromes. It includes the pathophysiology, diagnosis, diet, and definition of IBS, and contains many helpful statistics and graphs. Several other chapters within this book also relate directly to the cause of functional digestive disorders in addition to IBS, such as functional dyspepsia."
The Inside Tract, 2010; 175(2nd Quarter):16, reviewed by the Canadian Society of Intestinal Research

"The problem of all current therapies is the long-term follow up.  Do those patients perhaps need a live-time support and bounding?  Impressing improvements after therapy often melt after some time.  We still base our therapy on assumptions and patients with functional pain syndromes are often regarded as an unpopular group of clients, often misunderstood in the social and medical system.
 
"This is why this book indirectly makes a very important contribution also to the future management of patients with functional pain syndromes: it emphasizes the necessity of further research on these aspects and the authors point out which important facts have been already explored in the last years.  In summary, we really enjoyed the reading of this book and recommend it for any colleague who is interested in functional pain syndromes, both scientifically and clinically."
European Journal of Pain, 13 (2009) 1096, reviewed by Christian Maihöfner and Beatrix Vill (read full review)

“This book is stimulating and could catalyze the integration of atomized knowledge from end-organ-specialists into a contemporary version of body-mind-medicine.  I recommend it highly as a resource for basic reading and an orientation in the expanding research field.  The references are well organized and up-to-date."
International Musculoskeletal Medicine, 31(3), 2009, pp. 1-2, reviewed by Dr. Jens Foell (read full review)

"In 2001 Ray and Zbik published a chapter in Tollison's Practical Pain Management, WWW publishers, entitled Cognitive Behavioral Therapies and Beyond. At that time the term central sensitization had not yet become commonplace, and we were calling it central sensory dysfunction. We did recognize and link the same 'functional' problems together, as does your current book. What we tried to demonstrate is that these functional problems are due to sensitization issues (especially brain) and not peripheral end organ problems. They only produce symptoms in the end organ. I am so glad to see another book now linking these issues together, and we must again emphasize that we may be dealing with one 'genotype' (neural sensitization) with multiple 'phenotypes' (the individual syndromes we see, ie FM, IBS, Vulvodynia, etc.) Treatments need to be directed at the neuroplastic capabilities of the nervous system and not at the end organs. Norman Doidge's book The Brain That Changes Itself is a good beginning. The neuroplastic concepts, ie 'what is wired together stays together and what is wired apart stays apart', are the basis for how many of the non-pharmacological (and quite possibly some of the pharmacological as well) therapies work. Research needs to be extended further into this concept, if we are to be truly effective with some of these various syndromes. Keep up the good work, IASP."
Review by Albert Ray (May 6, 2009), member of IASP since 1978, posted through IASP Website

"After reading this book, physicians will be compelled to look at these conditions as part of malfunctioning pain system and not just as an isolated disease."
Doody's Book Review Service (Score: 86/100, 3/5 stars), reviewed by Tariq Malik, MD

"This is a timely and fascinating compilation of epidemiology, symptomatology, theories of mechanisms of pain, and a dollop of treatment recommendations.  A struggle is going on in the pain world involving those who believe that neuropathic pains must have a lesion or disease in the nervous system versus those who believe that dysfunction in the nervous system is all that is required for the diagnosis of neuropathic pain.  This book is firmly in the latter camp.  Each chapter is concise and highly focused upon a specific syndrome.  Evidence is marshaled in each argument to support the thesis that all of the functional pain syndromes are correlated with changes in the peripheral and central nervous system, and that these are all disorders of central neural processing.
 
"Interrelationships between functional syndromes are emphasized, as are the ties to affective states.  The final chapter, authored by the editors, attempts to synthesize the wisdom contained in the preceding [sic] 24 chapters and provides a complex set of hypotheses about these all-to-common reasons to seek health care.  This book is a good starting point for those who wish to know the current state of thought about these puzzling and costly human conditions."
APS Bulletin, Volume 19, Issue 2, 2009, Reviewed by John D. Loeser, MD

"Functional pain syndromes, including irritable bowel syndrome, fibromyalgia, and interstitial cystitis, affect up to 15% of the population worldwide.  This book brings together experts from the fields of pain medicine, gastroenterology, psychiatry, physiology, genetics, and neuroscience to review the growing evidence that these disorders have substantial comorbidity with each other."
SciTech Book News, September 2009 (Annotation © Book News Inc., Portland, OR www.booknews.com)

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