Skip to main content

Advertisement

SpringerLink
Log in

Fibromyalgia: An update and immunological aspects

  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Fibromyalgia syndrome (FMS) is now understood as a chronic pain syndrome, and recent evidence indicates it is not a pure psychosomatic disorder. We review the current knowledge in FMS pain pathways, focusing on the central system sensitization phenomenon and the abnormalities in the inhibitory pain systems. Chronic headache is one of the most common symptoms in FMS, and better knowledge of their common pathophysiologic features can help us understand both conditions better. These features include the nerve growth factor actions and failure of the endocannabinoid system. In addition, we review new immunological aspects of FMS, both in their humoral (autoantibodies, antipolymer antibodies) and cytokine (interleukin-2) aspects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Staud R: Biology and therapy of fibromyalgia: pain in fibromyalgia syndrome. Arthritis Res Ther 2006, 8:208.

    Article  PubMed  Google Scholar 

  2. Mendell LM, Wall PD: Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres. Nature 1965, 206:97–99.

    Article  PubMed  CAS  Google Scholar 

  3. Sorensen J, Bengtsson A, Ahlner J, et al.: Fibromyalgia—are there different mechanisms in the processing of pain? A double blind crossover comparison of analgesic drugs. J Rheumatol 1997, 24:1615–1621.

    PubMed  CAS  Google Scholar 

  4. Graven-Nielsen T, Aspegren Kendall S, Henriksson KG, et al.: Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients. Pain 2000, 85:483–491.

    Article  PubMed  CAS  Google Scholar 

  5. Sorensen J, Graven-Nielsen T, Henriksson KG, et al.: Hyperexcitability in fibromyalgia. J Rheumatol 1998, 25:152–155.

    PubMed  CAS  Google Scholar 

  6. Desmeules JA, Cedraschi C, Rapiti E, et al.: Neurophysiologic evidence for a central sensitization in patients with fibromyalgia. Arthritis Rheum 2003, 48:1420–1429.

    Article  PubMed  CAS  Google Scholar 

  7. Russell IJ, Orr MD, Littman B, et al.: Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum 1994, 37:1593–1601.

    Article  PubMed  CAS  Google Scholar 

  8. Larson AA, Giovengo SL, Russell IJ, Michalek JE: Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways. Pain 2000, 87:201–211.

    Article  PubMed  CAS  Google Scholar 

  9. Lorenz J, Grasedyck K, Bromm B: Middle and long latency somatosensory evoked potentials after painful laser stimulation in patients with fibromyalgia syndrome. Electroencephalogr Clin Neurophysiol 1996, 100:165–168.

    Article  PubMed  CAS  Google Scholar 

  10. Mountz JM, Bradley LA, Modell JG, et al.: Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum 1995, 38:926–938.

    Article  PubMed  CAS  Google Scholar 

  11. Gracely RH, Petzke F, Wolf JM, Clauw DJ: Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 2002, 46:1333–1343.

    Article  PubMed  Google Scholar 

  12. Russell IJ, Vaeroy H, Javors M, Nyberg F: Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum 1992, 35:550–556.

    Article  PubMed  CAS  Google Scholar 

  13. Wood PB, Schweinhardt P, Jaeger E, et al.: Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci 2007, 25:3576–3582.

    Article  PubMed  Google Scholar 

  14. Harris RE, Clauw DJ, Scott DJ, et al.: Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci 2007, 27:10000–10006.

    Article  PubMed  CAS  Google Scholar 

  15. Baraniuk JN, Whalen G, Cunningham J, Clauw DJ: Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain. BMC Musculoskelet Disord 2004, 5:48.

    Article  PubMed  CAS  Google Scholar 

  16. Staud R, Robinson ME, Vierck CJ Jr, Price DD: Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females or fibromyalgia patients. Pain 2003, 101:167–174.

    Article  PubMed  Google Scholar 

  17. Julien N, Goffaux P, Arsenault P, Marchand S: Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain 2005, 114:295–302.

    Article  PubMed  Google Scholar 

  18. Aaron LA, Buchwald D: Fibromyalgia and other unexplained clinical conditions. Curr Rheumatol Rep 2001, 3:116–122.

    Article  PubMed  CAS  Google Scholar 

  19. Aaron LA, Buchwald D: Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions. Best Pract Res Clin Rheumatol 2003, 17:563–574.

    Article  PubMed  Google Scholar 

  20. Cole JA, Yeaw JM, Cutone JA, et al.: The incidence of abdominal and pelvic surgery among patients with irritable bowel syndrome. Dig Dis Sci 2005, 50:2268–2275.

    Article  PubMed  Google Scholar 

  21. Marcus DA, Bernstein C, Rudy TE: Fibromyalgia and headache: an epidemiological study supporting migraine as part of the fibromyalgia syndrome. Clin Rheumatol 2005, 24:595–601.

    Article  PubMed  Google Scholar 

  22. Ifergane G, Buskila D, Simiseshvely N, et al.: Prevalence of fibromyalgia syndrome in migraine patients. Cephalalgia 2006, 26:451–456.

    Article  PubMed  CAS  Google Scholar 

  23. Centonze V, Bassi A, Cassiano MA, et al.: Migraine, daily chronic headache and fibromyalgia in the same patient: an evolutive “continuum”; of non organic chronic pain? About 100 clinical cases. Neurol Sci 2004, 25(Suppl 3):S291–S292.

    Article  PubMed  Google Scholar 

  24. Sarchielli P, Di Filippo M, Nardi K, Calabresi P: Sensitization, glutamate, and the link between migraine and fibromyalgia. Curr Pain Headache Rep 2007, 11:343–351.

    Article  PubMed  Google Scholar 

  25. Peres MF, Zukerman E, Senne Soares CA, et al.: Cerebrospinal fluid glutamate levels in chronic migraine. Cephalalgia 2004, 24:735–739.

    Article  PubMed  CAS  Google Scholar 

  26. Russo EB: Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett 2008, 29:192–200.

    PubMed  Google Scholar 

  27. Felson DT, Goldenberg DL: The natural history of fibromyalgia. Arthritis Rheum 1986, 29:1522–1526.

    Article  PubMed  CAS  Google Scholar 

  28. Inaninci F, Yunus MB: History of fibromyalgia: past to present. Curr Pain Headache Rep 2004, 8:369–378.

    Article  Google Scholar 

  29. Dinerman H, Goldenberg DL, Felson DT: A prospective evaluation of 118 patients with the fibromyalgia syndrome: prevalence of Raynaud’s phenomenon, sicca symptoms, ANA, low complement, and Ig deposition at the dermalepidermal junction. J Rheumatol 1986, 13:368–373.

    PubMed  CAS  Google Scholar 

  30. Caro XJ: Immunofluorescent detection of IgG at the dermal-epidermal junction in patients with apparent primary fibrositis syndrome. Arthritis Rheum 1984, 27:1174.

    Article  PubMed  CAS  Google Scholar 

  31. Jacobsen S, Høyer-Madsen M, Danneskiold-Samsøe B, Wiik A: Screening for autoantibodies in patients with primary fibromyalgia syndrome and a matched control group. APMIS 1990, 98:655–658

    Article  PubMed  CAS  Google Scholar 

  32. Yunus MB, Hussey FX, Aldag JC: Antinuclear antibodies and connective tissue disease features in fibromyalgia syndrome: a controlled study. J Rheumatol 1993, 20:1557–1560.

    PubMed  CAS  Google Scholar 

  33. Nash P, Chard M, Hazleman B: Chronic coxsackie B infection mimicking primary fibromyalgia. J Rheumatol 1989, 16:1506–1508.

    PubMed  CAS  Google Scholar 

  34. Leventhal LJ, Naides SJ, Freundlich B: Fibromyalgia and parvovirus infection. Arthritis Rheum 1991, 34:1319–1324.

    Article  PubMed  CAS  Google Scholar 

  35. Dinerman H, Steere AC: Lyme disease associated with fibromyalgia. Ann Intern Med 1992, 117:281–285.

    PubMed  CAS  Google Scholar 

  36. Hsu VM, Patella S, Sigal LH: “Chronic Lyme disease” as the incorrect diagnosis in patients with fibromyalgia. Arthritis Rheum 1993, 36:1493–1500.

    Article  PubMed  CAS  Google Scholar 

  37. Buskila D, Gladman DD, Langevitz P, et al.: Fibromyalgia in human immunodeficiency virus infection. J Rheumatol 1990, 17:1202–1206.

    PubMed  CAS  Google Scholar 

  38. Tenenbaum SA, Rice JC, Espinoza LR, et al.: Use of antipolymer antibody assay in recipients of silicone breast implants. Lancet 1997, 349:449–454.

    Article  PubMed  CAS  Google Scholar 

  39. Wilson RB, Gluck OS, Tesser JR, et al.: Antipolymer antibody reactivity in a subset of patients with fibromyalgia correlates with severity. J Rheumatol 1999, 26:402–407.

    PubMed  CAS  Google Scholar 

  40. Lee SS, Yoon HJ, Park YW: Antipolymer antibody is not associated with fibromyalgia in Korean female patients. Rheumatol Int 2006, 27:73–77.

    Article  PubMed  CAS  Google Scholar 

  41. Jensen B, Wittrup IH, Wiik A, et al.: Antipolymer antibodies in Danish fibromyalgia patients. Clin Exp Rheumatol 2004, 22:227–229.

    PubMed  CAS  Google Scholar 

  42. Bazzichi L, Giacomelli C, De Feo F, et al.: Antipolymer antibody in Italian fibromyalgic patients. Arthritis Res Ther 2007, 9:R86.

    Article  PubMed  CAS  Google Scholar 

  43. Sarzi-Puttini P, Atzeni F, Di Franco M, et al.: Anti-polymer antibodies are correlated with pain and fatigue severity in patients with fibromyalgia syndrome. Autoimmunity 2008, 41:74–79.

    Article  PubMed  CAS  Google Scholar 

  44. Kötter I, Neuscheler D, Günaydin I, et al.: Is there a predisposition for the development of autoimmune diseases in patients with fibromyalgia? Retrospective analysis with long term follow-up. Rheumatol Int 2007, 27:1031–1039.

    Article  PubMed  Google Scholar 

  45. Pamuk ON, Cakir N: The frequency of thyroid antibodies in fibromyalgia patients and their relationship with symptoms. Clin Rheumatol 2007, 26:55–59.

    Article  PubMed  Google Scholar 

  46. Ribeiro LS, Proietti FA: Interrelations between fibromyalgia, thyroid autoantibodies, and depression. J Rheumatol 2004, 31:2036–2040.

    PubMed  Google Scholar 

  47. Bazzichi L, Rossi A, Giuliano T, et al.: Association between thyroid autoimmunity and fibromyalgic disease severity. Clin Rheumatol 2007, 26:2115–2120.

    Article  PubMed  Google Scholar 

  48. Romano TJ: Possible concomitant fibromyalgia in systemic lupus erythematosus patients with overt central nervous system disease but with cognitive deficits: comment on the article by Kozora et al. Arthritis Rheum 1997, 40:1544–1545.

    Article  PubMed  CAS  Google Scholar 

  49. Wolfe F, Michaud K: Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize RA patients with fibromyalgia. J Rheumatol 2004, 31:695–700.

    PubMed  Google Scholar 

  50. Buskila D, Sarzi-Puttini P: Fibromyalgia and autoimmune diseases: the pain behind autoimmunity. Isr Med Assoc J 2008, 10:77–78.

    PubMed  Google Scholar 

  51. Ranshoff RM, Benveniste EN: Cytokines and the Central Nervous System. New York: Taylor and Francis; 2006.

    Google Scholar 

  52. Wallace DJ, Margolin K, Waller P: Fibromyalgia and interleukin-2 therapy for malignancy. Ann Intern Med 1988, 108:909.

    PubMed  CAS  Google Scholar 

  53. Uçeyler N, Valenza R, Stock M, et al.: Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum 2006, 54:2656–2664.

    Article  PubMed  CAS  Google Scholar 

  54. Wallace DJ, Linker-Israeli M, Hallegua D, et al.: Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study. Rheumatology (Oxford) 2001, 40:743–749.

    Article  CAS  Google Scholar 

  55. Gür A, Karakoç M, Nas K, et al.: Cytokines and depression in cases with fibromyalgia. J Rheumatol 2002, 29:358–361.

    PubMed  Google Scholar 

  56. Macedo JA, Hesse J, Turner JD, et al.: Adhesion molecules and cytokine expression in fibromyalgia patients: increased L-selectin on monocytes and neutrophils. J Neuroimmunol 2007, 188:159–166.

    Article  PubMed  CAS  Google Scholar 

  57. Bazzichi L, Rossi A, Massimetti G, et al.: Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Clin Exp Rheumatol 2007, 25:225–230.

    PubMed  CAS  Google Scholar 

  58. Yunus MB, Khan MA, Rawlings KK, et al.: Genetic linkage analysis of multicase families with fibromyalgia syndrome. J Rheumatol 1999, 26:408–412.

    PubMed  CAS  Google Scholar 

  59. Peres MF: Fibromyalgia fatigue and headache disorders. Curr Neurol Neurosci Rep 2003, 3:97–103.

    Article  PubMed  Google Scholar 

  60. Peres MF, Young WB, Kaup AO, et al.: Fibromyalgia is common in patients with transformed migraine. Neurology 2001, 57:1326–1328.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Physician and Research Associate Hospital Israelita Albert Einstein and Research Institute, Av. Albert Einstein 627, Sao Paulo, Brazil

    Morton Scheinberg

  2. Scientific Director and Head of Clinical Research, Hospital Abreu Sodre-AACD, Sao Paulo, Brazil

    Morton Scheinberg

Authors
  1. Eduardo S. Paiva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evelin Diana Goldenberg Mariano da Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Morton Scheinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Morton Scheinberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paiva, E.S., Mariano da Costa, E.D.G. & Scheinberg, M. Fibromyalgia: An update and immunological aspects. Current Science Inc 12, 321–326 (2008). https://doi.org/10.1007/s11916-008-0054-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11916-008-0054-x

Keywords

Search

Navigation