Fibromyalgia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

The exact cause of fibromyalgia is unknown. Multiple factors are believed to influence the development of fibromyalgia. Various hypotheses have been offered describing the pathogenesis of fibromyalgia. It is understood that Lyme disease may be a trigger of the symptoms of fibromyalgia. It is suggested that more than one clinical entity may be involved in the pathogenesis of fibromyalgia, ranging from a mild, idiopathic inflammatory process to clinical depression.[1][2]

Pathophysiology

The exact cause of fibromyalgia is unknown. Multiple factors are believed to influence the development of fibromyalgia. Various hypotheses have been offered describing the pathogenesis of fibromyalgia. It is understood that Lyme disease may be a trigger of the symptoms of fibromyalgia. It is suggested that more than one clinical entity may be involved in the pathogenesis of fibromyalgia, ranging from a mild, idiopathic inflammatory process to clinical depression.[3][4]

Stress

  • Stress is a significant precipitating factor in the development of fibromyalgia.[5][6][7]
  • A non-mainstream hypothesis is that fibromyalgia may be a psychosomatic illness, described by John E. Sarno's "tension myositis syndrome."
  • Sarno believes many cases of chronic pain result from changes in the body caused by the mind's subconscious strategy of distracting painful or dangerous emotions.
  • Education, attitude change, (and in some cases, psychotherapy) are treatments proposed to stop the brain from using negative strategies to process painful emotions.[8][9]
  • Robert G. Schwartz, MD, proposed an alternative view in which mind-body connections may play an important role in chronic disease (not just fibromyalgia).

Dopamine abnormality

Serotonin

Sleep disturbance

  • The sleep disturbance hypothesis states that any event such as a trauma or illness that causes sleep disturbance and chronic pain may initiate fibromyalgia.
  • According to the hypothesis, stage 4 sleep is critical for normal functioning of the nervous system because, in stage 4 sleep, certain neurochemical processes in the body "reset."
  • It is during that stage 4 sleep, pain causes the release of the neuropeptide substance P in the spinal cord, which leads to amplification of pain and nerves to become more sensitive to pain.
  • If pain becomes chronic and systemic, this process can run out of control.
  • The sleep disturbance hypothesis holds that deep sleep is critical to reset the substance P mechanism and prevent this out-of-control effect.
  • The sleep disturbance/substance P hypothesis could explain "tender points" that are characteristic of fibromyalgia but which are otherwise enigmatic since their positions don't correspond to any particular set of nerve junctions or other obvious body structures.
  • The sleep disturbance hypothesis proposes that these locations are more sensitive because the sensory nerves that serve them are positioned in the spinal cord to be most strongly affected by substance P.
  • The sleep disturbance hypothesis could also explain some of more general neurological features of fibromyalgia since substance P is active in many other areas of the nervous system.
  • The sleep disturbance hypothesis could also explain a possible connection between fibromyalgia, chronic fatigue syndrome (CFS), and post-polio syndrome through damage to the ascending reticular activating system of the reticular formation.
    • This area of the brain, in addition to apparently controlling the sensation of fatigue, is known to control sleep behaviors and is also believed to produce some neuropeptides. Thus, injury or imbalance in this area could cause both CFS and sleep-related fibromyalgia.
  • Electroencephalography studies have shown that people with fibromyalgia lack slow-wave sleep and circumstances that interfere with stage four sleep (pain, depression, serotonin deficiency, certain medications or anxiety) may cause or worsen the condition.

Human growth hormone

Deposition disease

  • The deposition hypothesis of fibromyalgia states that fibromyalgia is due to intracellular phosphate and calcium accumulations that eventually reach levels sufficient to impede the ATP process. This may be caused by a kidney defect or missing enzyme that prevents the removal of excess phosphates from the bloodstream.
  • Proponents of this hypothesis suggest that fibromyalgia may be an inherited disorder and that phosphate buildup in cells is gradual but can be accelerated by trauma or illness.
  • Calcium is required for the excess phosphate to enter the cells. The additional phosphate slows down the ATP process; however, the excess calcium stimulates the cell to continue producing ATP.
  • The phosphate build-up hypothesis explains many of the symptoms present in fibromyalgia and proposes an underlying cause.

Other hypotheses

Associated Conditions

Genetics

By using self-reported "Chronic Widespread Pain" (CWP) as a surrogate marker for fibromyalgia, the Swedish Twin Registry found that a modest genetic contribution may exist:[42][43]

References

  1. http://www.springerlink.com/content/1271314042w8405g/ Mueller W, et al. The classification of fibromyalgia syndrome. Rheumatol Int. 2007 Jul 25
  2. "Late and Chronic Lyme Disease: Symptom Overlap with Chronic Fatigue Syndrome & Fibromyalgia".
  3. http://www.springerlink.com/content/1271314042w8405g/ Mueller W, et al. The classification of fibromyalgia syndrome. Rheumatol Int. 2007 Jul 25
  4. "Late and Chronic Lyme Disease: Symptom Overlap with Chronic Fatigue Syndrome & Fibromyalgia".
  5. Anderberg UM, Marteinsdottir I, Theorell T, von Knorring L. "The impact of life events in female patients with fibromyalgia and in female healthy controls". Eur Psychiatry. 15 (5): 33–41. PMID 10954873.
  6. Amital D, Fostick L, Polliack ML, Segev S, Zohar J, Rubinow A, Amital H. "Posttraumatic stress disorder, tenderness, and fibromyalgia syndrome: are they different entities?". J Psychosom Res. 61 (5): 663–9. PMID 17084145.
  7. Raphael KG, Janal MN, Nayak S. "Comorbidity of fibromyalgia and posttraumatic stress disorder symptoms in a community sample of women". Pain Med. 5 (1): 33–41. PMID 14996235.
  8. Sarno, Dr. John E, (1998). The Mindbody Prescription: Healing the Body, Healing the Pain. pp. 76–78. ISBN 0-446-67515-6.
  9. Sarno, Dr. John E. et al, (2006). The Divided Mind: The Epidemic of Mindbody Disorders. pp. 21–22, 235–237, 294–298. ISBN 0-06-085178-3.
  10. The role of life stress in fibromyalgia. [Curr Rheumatol Rep. 2005] - PubMed Result
  11. Chronic widespread pain and fibromyalgia: what we ...[Best Pract Res Clin Rheumatol. 2003] - PubMed Result
  12. Stress and dopamine: implications for the pathophy...[Med Hypotheses. 2004] - PubMed Result
  13. Dopamine-containing neurons in the spinal cord: an...[Ann Neurol. 1983] - PubMed Result
  14. Direct inhibition of substantia gelatinosa neurones in the rat spinal cord by activation of dopamine D2-like receptors
  15. The effects of stress on central dopaminergic neur...[Neurochem Res. 1997] - PubMed Result
  16. The role of the basal ganglia in nociception and p...[Pain. 1995] - PubMed Result
  17. The role of dopamine in the nucleus accumbens in a...[Life Sci. 1999] - PubMed Result
  18. Dopamine Reuptake Inhibition in the Rostral Agranular Insular Cortex Produces Antinociception - Burkey et al. 19 (10): 4169 - Journal of Neuroscience
  19. Dopamine and NMDA systems modulate long-term nocic...[Pain. 2004] - PubMed Result
  20. Neurophysiological, pharmacological and behavioral...[Brain Res. 1992] - PubMed Result
  21. Opiate anti-nociception is attenuated following le...[Pain. 2004] - PubMed Result
  22. Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study - Yunus and Aldag 312 (7042): 1339 - BMJ
  23. Support for dopaminergic hypoactivity in restless ...[Brain. 2006] - PubMed Result
  24. Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome - Stiasny-Kolster et al. 127 (4): 773 - Brain
  25. Platelet 3H-imipramine uptake receptor density and...[J Rheumatol. 1992] - PubMed Result
  26. Cerebrospinal fluid biogenic amine metabolites in ...[Arthritis Rheum. 1992] - PubMed Result
  27. McCall-Hosenfeld JS, Goldenberg DL, Hurwitz S, Adler GK (2003). "Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia". J. Rheumatol. 30 (4): 809–14. PMID 12672204.
  28. Anderberg UM, Liu Z, Berglund L, Nyberg F (1999). "Elevated plasma levels of neuropeptide Y in female fibromyalgia patients". Eur J Pain. 3 (1): 19–30. doi:10.1053/eujp.1998.0097. PMID 10700334.
  29. Jones KD, Deodhar P, Lorentzen A, Bennett RM, Deodhar AA (2007). "Growth hormone perturbations in fibromyalgia: a review". Semin. Arthritis Rheum. 36 (6): 357–79. doi:10.1016/j.semarthrit.2006.09.006. PMID 17224178.
  30. Shuer, ML. "Fibromyalgia: symptom constellation and potential therapeutic options". Endocrine. 22 (1): 67–76. PMID 14610300.
  31. Yuen KC, Bennett RM, Hryciw CA, Cook MB, Rhoads SA, Cook DM (2007). "Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?". Growth Horm. IGF Res. 17 (1): 82–8. doi:10.1016/j.ghir.2006.12.006. PMID 17289417.
  32. Bennett RM, Cook DM, Clark SR, Burckhardt CS, Campbell SM (1997). "Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia". J. Rheumatol. 24 (7): 1384–9. PMID 9228141.
  33. Kendall SN. "Remission of rosacea induced by reduction of gut transit time". Clin Exp dermatol. 29 (3): 297–9. PMID 15115515.
  34. Pimental M, Wallace D, Hallegua D et .al. "A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing". Ann Rheum Dis. 63 (4): 450–2. PMID 15020342.
  35. Brown SL, Pennello G, Berg WA, Soo MS, Middleton MS (2001). "Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women". J Rheumatol. 28 (5): 996–1003. PMID 11361228.
  36. "Study of Silicone Gel Breast Implant Rupture, Extracapsular Silicone, and Health Status in a Population of Women". FDA. May 29, 2001.
  37. "FDA Breast Implant Consumer Handbook 2004". FDA. June 8, 2004.
  38. Lipworth L, Tarone RE, McLaughlin JK. (2004). "Breast implants and fibromyalgia: a review of the epidemiological evidence". Ann Plast Surg. 52 (3): 284–7. PMID 15156983.
  39. Katz DL, Greene L, Ali A, Faridi Z. "The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation". Med Hypotheses. (Epub ahead of print). doi:10.1016/j.mehy.2005.10.037. PMID 17376601.
  40. Frissora CL, Koch KL (2005). "Symptom overlap and comorbidity of irritable bowel syndrome with other conditions". Current gastroenterology reports. 7 (4): 264–71. PMID 16042909.
  41. Zipser RD, Patel S, Yahya KZ, Baisch DW, Monarch E (2003). "Presentations of adult celiac disease in a nationwide patient support group". Dig. Dis. Sci. 48 (4): 761–4. PMID 12741468.
  42. Kato K, Sullivan P, Evengård B, Pedersen N (2006). "Importance of genetic influences on chronic widespread pain". Arthritis Rheum. 54 (5): 1682–6. doi:10.1002/art.21798. PMID 16646040.
  43. Kato K, Sullivan P, Evengård B, Pedersen N (2006). "Chronic widespread pain and its comorbidities: a population-based study". Arch. Intern. Med. 166 (15): 1649–54. PMID 16908799.