Pathophysiology of Fibromyalgia

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Abstract

This article reviews the biologic, genetic, and environmental factors that may contribute to the pathophysiology of fibromyalgia. As an affective spectrum disorder, fibromyalgia may share these causal factors with a number of related and co-occurring pain conditions, such as irritable bowel syndrome or temporomandibular disorder. There is strong evidence that cardinal pain symptoms of fibromyalgia may be due to alterations in central processing of sensory input, along with aberrations in the endogenous inhibition of pain. Genetic research has shown familial aggregation of fibromyalgia and other related disorders such as major depressive disorder. Exposure to physical or psychosocial stressors, as well as abnormal biologic responses in the autonomic nervous system and neuroendocrine responses, may also contribute to dysfunctional pain processing. As fibromyalgia research continues to progress, it is expected that the pathophysiology of this disorder will be further elucidated, leading to more rational and targeted strategies for the treatment of patients with this condition.

Section snippets

Abnormal Pain Sensitivity and Pain Inhibition in Fibromyalgia

Patients with fibromyalgia display enhanced sensitivity to a wide array of stimuli, such as heat and cold, as well as to mechanical and ischemic pressure. These stimuli produce pain responses in patients when applied at levels of intensity that do not evoke pain responses in healthy individuals.7 There is increasing evidence that fibromyalgia is characterized by an augmentation of sensory input that is mediated by central nervous system (CNS) events similar to those associated with neuropathic

Neuroendocrine System

Fibromyalgia is generally considered to be a stress-related disorder that involves abnormal functioning in the hypothalamic-pituitary-adrenal (HPA) axis. Similarly to psychiatric disorders, fibromyalgia has been associated with the inability to suppress cortisol. In a study conducted by McCain and Tilbe,18 for example, it was found that compared with patients with RA, patients with fibromyalgia displayed significantly higher overall plasma cortisol (P <0.001) and exhibited higher peak and

Genetic Evidence for ASDs

Recent studies2, 3, 31 in patients with fibromyalgia, RA, or MDD, as well as the first-degree relatives of these individuals, support the ASD hypothesis that certain related disorders may share genetic risk factors. Arnold and colleagues,3 for example, reported that compared with the first-degree relatives of patients with RA, the relatives of patients with fibromyalgia more frequently met the diagnostic criteria for fibromyalgia or MDD and exhibited a greater number of sensitive anatomic sites

Environmental Triggers

Environmental triggers that may be involved in the pathophysiology of fibromyalgia include mechanical/physical trauma or injury and psychosocial stressors.60, 61, 62 Commonly reported physical traumas include acute illness, physical injury, surgery, and motor vehicle accidents. Commonly reported psychosocial triggers include chronic stress, emotional trauma, and emotional, physical, or sexual abuse.63 The effects of psychosocial stressors may be especially pervasive because, in addition to

Summary

Factors contributing to the pathophysiology of fibromyalgia include abnormal function of the autonomic and neuroendocrine systems, genetic influences, and environmental triggers such as exposure to stressors. These factors usually are also associated with disorders that co-occur or overlap with fibromyalgia, such as MDD, IBS, and TMD. Alterations in central processing of sensory input and deficits in endogenous pain inhibition may also contribute to the enhanced pain sensitivity and persistence

Author Disclosures

  • The author of this article has disclosed the following industry relationships:

  • Laurence A. Bradley, PhD, is a member of the Speakers' Bureau for Eli Lilly and Company and Forest Laboratories, Inc.; works as a consultant to Eli Lilly and Company and Forest Laboratories, Inc.; and serves on the advisory boards of Eli Lilly and Company and Forest Laboratories, Inc.

Acknowledgment

Editorial assistance was provided by Prescott Medical Communications Group, Chicago, Illinois.

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    Statement of author disclosure: Please see the Author Disclosures section at the end of this article.

    Dr. Bradley has received grant/research support from the National Institutes of Health (NIH), the Agency for Healthcare Research and Quality (AHRQ), and the American Fibromyalgia Syndrome Association (AFSA).

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