Skip to main content

Fibromyalgia: Present to future

Abstract

There has been a dramatic increase in our understanding of fibromyalgia throughout the past 14 years since the publica-tion of the 1990 American College of Rheumatology classi-fication criteria. Before 1990, and for most of the 20th century, fibromyalgia was considered to be predominantly a muscle disorder; now the critical abnormality is described as "central sensitization." However, central sensitization has to have an initial genesis and nociceptive stimuli from painful foci in muscle are increasingly recognized as being relevant to the development of fibromyalgia. Clinicians also recognize an association between the initiation of fibromy-algia and chronic psychologic stressors and inflammatory disorders. It has been more difficult to understand how two such apparently diverse events could affect central pain physiology. However, some clues are emerging from the role of diverse stimuli in activating glial cells and the role of disordered cytokine networks. Some predictions about future developments in fibromyalgia are ventured based on the current state of knowledge.

This is a preview of subscription content, access via your institution.

References and Recommended Reading

  1. Staud R: Evidence of involvement of central neural mecha-nisms in generating fibromyalgia pain. Curr Rheumatol Rep 2002, 4:299–305. A concise, up-to-date review of the evidence of central sensitization and fibromyalgia.

    PubMed  Article  Google Scholar 

  2. Wolfe F, Smythe HA, Yunus MB, et al.: The American College of Rheumatology 1990 criteria for the classification of fibromy-algia: report of the Multicenter Criteria Committee. Arthritis Rheum 1990, 33:160–172.

    PubMed  Article  CAS  Google Scholar 

  3. Smythe HA, Moldofsky H: Two contributions to understand-ing of the "fibrositis" syndrome. Bull Rheum Dis 1977, 28:928–931.

    PubMed  Google Scholar 

  4. Neumann L, Buskila D: Epidemiology of fibromyalgia. Curr Pain Headache Rep 2003, 7:362–368.

    PubMed  Google Scholar 

  5. Croft P, Burt J, Schollum J, et al.: More pain, more tender points: Is fibromyalgia just one end of a continuous spec-trum? Ann Rheum Dis 1996, 55:482–485.

    PubMed  CAS  Article  Google Scholar 

  6. Desmeules JA, Cedraschi C, Rapiti E, et al.: Neurophysiologic evidence for a central sensitization in patients with fibromy-algia. Arthritis Rheum 2003, 48:1420–1429. The first report of using the nociceptive flexion reflex to demonstrate central sensitization in fibromyalgia subjects.

    PubMed  Article  CAS  Google Scholar 

  7. Staud R: Fibromyalgia pain: Do we know the source? Curr Opin Rheumatol 2004, 16:157–163.

    PubMed  Article  Google Scholar 

  8. Wall PD, Woolf CJ: Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flex-ion reflex in the rat. J Physiol 1984, 356:443–458.

    PubMed  CAS  Google Scholar 

  9. Staud R, Cannon RC, Mauderli AP, et al.: Temporal summation of pain from mechanical stimulation of muscle tissue in nor-mal controls and subjects with fibromyalgia syndrome. Pain 2003, 102:87–95. An important paper that demonstrates an increased wind-up phenomena in patients with fibromyalgia compared with healthy control subjects.

    PubMed  Article  Google Scholar 

  10. Jubrias SA, Bennett RM, Klug GA: Increased incidence of a resonance in the phosphodiester region of 31P nuclear magnetic resonance spectra in the skeletal muscle of fibromyalgia patients. Arthritis Rheum 1994, 37:801–807.

    PubMed  Article  CAS  Google Scholar 

  11. Arendt-Nielsen L, Graven-Nielsen T: Central sensitization in fibromyalgia and other musculoskeletal disorders. Curr Pain Headache Rep 2003, 7:355–361.

    PubMed  Google Scholar 

  12. Sprott H, Salemi S, Gay RE, et al.: Increased DNA fragmenta-tion and ultrastructural changes in fibromyalgic muscle fibers. Ann Rheum Dis 2004, 63:245–251.

    PubMed  Article  CAS  Google Scholar 

  13. Mense S: The pathogenesis of muscle pain. Curr Pain Headache Rep 2003, 7:419–425.

    PubMed  Google Scholar 

  14. Watkins LR, Maier SF: Implications of immune-to-brain com-munication for sickness and pain. Proc Natl Acad Sci U S A 1999, 96:7710–7713. A classical review of the role of cytokines and glial cells in the patho-genesis of pain states.

    PubMed  Article  CAS  Google Scholar 

  15. Watkins LR, Milligan ED, Maier SF: Glial activation: a driving force for pathological pain. Trends Neurosci 2001, 24:450–455.

    PubMed  Article  CAS  Google Scholar 

  16. Obata K, Noguchi K: MAPK activation in nociceptive neurons and pain hypersensitivity. Life Sci 2004, 74:2643–2653.

    PubMed  Article  CAS  Google Scholar 

  17. Arici A: Local cytokines in endometrial tissue: the role of interleukin-8 in the pathogenesis of endometriosis. Ann N Y Acad Sci 2002, 955:101–109; discussion 118, 396–406.

    PubMed  CAS  Article  Google Scholar 

  18. Bajaj P, Bajaj P, Madsen H, Arendt-Nielsen L: Endometriosis is associated with central sensitization: a psychophysical con-trolled study. J Pain 2003, 4:372–380.

    PubMed  Article  Google Scholar 

  19. Trysberg E, Carlsten H, Tarkowski A: Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus 2000, 9:498–503.

    PubMed  Article  CAS  Google Scholar 

  20. Uveges JM, Parker JC, Smarr KL: Psychological symptoms in pri-mary fibromyalgia syndrome: relationship to pain, life stress, and sleep disturbance. Arthritis Rheum 1990, 33:1279–1283.

    PubMed  CAS  Article  Google Scholar 

  21. Boscarino JA: Diseases among men 20 years after exposure to severe stress: implications for clinical research and medical care. Psychosom Med 1997, 59:605–614.

    PubMed  CAS  Google Scholar 

  22. Amir M, Kaplan Z, Neumann L, et al.: Post-traumatic stress disorder, tenderness, and fibromyalgia. J Psychosom Res 1997, 42:607–613.

    PubMed  Article  CAS  Google Scholar 

  23. Cohen H, Neumann L, Haiman Y, et al.: Prevalence of post-traumatic stress disorder in fibromyalgia patients: overlap-ping syndromes or post-traumatic fibromyalgia syndrome? Semin Arthritis Rheum 2002, 32:38–50.

    PubMed  Article  Google Scholar 

  24. Volpato S, Guralnik JM, Ferrucci L, et al.: Cardiovascular disease, interleukin-6, and risk of mortality in older women: the women’s health and aging study. Circulation 2001, 103:947–953.

    PubMed  CAS  Google Scholar 

  25. Adler GK, Kinsley BT, Hurwitz S, et al.: Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome. Am J Med 1999, 106:534–543.

    PubMed  Article  CAS  Google Scholar 

  26. Bremner JD, Vythilingam M, Anderson G, et al.: Assessment of the hypothalamic-pituitary-adrenal axis over a 24-hour diur-nal period and in response to neuroendocrine challenges in women with and without childhood sexual abuse and post-traumatic stress disorder. Biol Psychiatry 2003, 54:710–718.

    PubMed  Article  CAS  Google Scholar 

  27. Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, et al.: Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci U S A 2003, 100:9090–9095.

    PubMed  Article  CAS  Google Scholar 

  28. Capuron L, Hauser P, Hinze-Selch D, et al.: Treatment of cytokine-induced depression. Brain Behav Immun 2002, 16:575–580.

    PubMed  Article  CAS  Google Scholar 

  29. Altier N, Stewart J: The role of dopamine in the nucleus accumbens in analgesia. Life Sci 1999, 65:2269–2287.

    PubMed  Article  CAS  Google Scholar 

  30. Altier N, Stewart J: Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine. J Pharmacol Exp Ther 1998, 285:208–215.

    PubMed  CAS  Google Scholar 

  31. Wood PB: Stress and dopamine: implications for the pathophysiology of chronic widespread pain. Med Hypotheses 2004, 62:420–424.

    PubMed  Article  CAS  Google Scholar 

  32. Ji RR: Mitogen-activated protein kinases as potential targets for pain killers. Curr Opin Investig Drugs 2004, 5:71–75.

    PubMed  Google Scholar 

  33. Arnold LM, Hudson JI, Hess EV, et al.: Family study of fibromy-algia. Arthritis Rheum 2004, 50:944–952. An important paper documenting a strong familial aggregation of fibromyalgia and a coaggregation with depression.

    PubMed  Article  Google Scholar 

  34. Ehrlich GE: Pain is real; fibromyalgia isn’t. J Rheumatol 2003, 30:1666–1667.

    PubMed  Google Scholar 

  35. Owens MJ, Nemeroff CB: Role of serotonin in the pathophysi-ology of depression: focus on the serotonin transporter. Clin Chem 1994, 40:288–295.

    PubMed  CAS  Google Scholar 

  36. Cohen H, Buskila D, Neumann L, Ebstein RP: Confirmation of an association between fibromyalgia and serotonin trans-porter promoter region (5-HTTLPR) polymorphism, and relationship to anxiety-related personality traits. Arthritis Rheum 2002, 46:845–847.

    PubMed  Article  Google Scholar 

  37. Offenbaecher M, Bondy B, de Jonge S, et al.: Possible associa-tion of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region. Arthritis Rheum 1999, 42:2482–2488.

    PubMed  Article  CAS  Google Scholar 

  38. Gursoy S: Absence of association of the serotonin transporter gene polymorphism with the mentally healthy subset of fibromyalgia patients. Clin Rheumatol 2002, 21:194–197.

    PubMed  Article  Google Scholar 

  39. Arnold LM, Iyenger SK, Kahn MA, et al.: Genetic linkage of fibromyalgia to the serotonin receptor 2A region on chromo-some 513 [Abstract 108]. Arthritis Rheum 2003, 48(suppl).

  40. Gursoy S, Erdal E, Herken H, et al.: Association of T102C poly-morphism of the 5-HT2A receptor gene with psychiatric sta-tus in fibromyalgia syndrome. Rheumatol Int 2001, 21:58–61.

    PubMed  Article  CAS  Google Scholar 

  41. Zubieta JK, Heitzeg MM, Smith YR, et al.: COMT val 158 met gen-otype affects mu-opioid neurotransmitter responses to a pain stressor. Science 2003, 299:1240–1243.

    PubMed  Article  CAS  Google Scholar 

  42. Gursoy S, Erdal E, Herken H, et al.: Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syn-drome. Rheumatol Int 2003, 23:104–107.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bennett, R. Fibromyalgia: Present to future. Curr Rheumatol Rep 7, 371–376 (2005). https://doi.org/10.1007/s11926-005-0022-y

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-005-0022-y

Keywords

  • Endometriosis
  • Fibromyalgia
  • Nucleus Accumbens
  • Familial Mediterranean Fever
  • Central Sensitization