[Editor's Note: This article was originally presented as an independent educational activity under the direction of CME LLC. The testing period to receive CME credits has expired. The article is now presented here for your reference. CME LLC does not review this content to ensure its continued relevance.]
Educational Objectives—After reading this article, you will be familiar with:
• The symptoms that constitute fibromyalgia.
• The proposed pathophysiology of fibromyalgia.
• The affective, behavioral, and cognitive factors that contribute to fibromyalgia.
• The available options for treating symptoms of fibromyalgia.
Who will benefit from reading this article?
Psychiatrists, neurologists, primary care physicians, geriatricians, nurse practitioners, and other health care professionals. Continuing medical education credit is available for most specialists. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing board.
Fibromyalgia syndrome (FM) is a chronic condition that consists of a pervasive set of unexplained physical symptoms with widespread pain (involving at least 3 of 4 body quadrants and axials) of at least 3 months duration and point tenderness at 9 bilateral locations (Figure) as the cardinal features.1 Patients with FM report a set of symptoms, functional limitations, and psychological dysfunctions, including persistent fatigue (78.2%), sleep disturbance (75.6%), feelings of stiffness (76.2%), headaches (54.3%), depression and anxiety (44.9%), and irritable bowel disorders (35.7%).1 Patients also report cognitive impairment and general malaise, “fibro fog.” This pattern of symptoms has been reported under various names (such as tension myalgia, psychogenic rheumatism, and fibromyositis) since the early 19th century.
In the United States, there are an estimated 3 to 6 million people who have FM.2 The condition is more common in women: the ratio of women to men who seek treatment is approximately 7 to 1. Community samples are closer to 3 to 1. The number of diagnoses of FM tends to increase from the second through the sixth decade of life.
FM may have an insidious onset without an identifiable cause, may develop following a flu-like illness, or may rapidly develop following a physical trauma (such as a motor vehicle accident).3 The natural course of FM symptoms seems to be chronic and nonprogressive; symptoms fluctuate in severity and are often exacerbated by stress. Patients with FM report a diminished sense of physical well-being; they have significant health concerns and are high users of the health care system.4
PATHOPHYSIOLOGY
The pathophysiological mechanisms that underlie FM are poorly understood. There is no accepted biological marker, and the results of radiographic and laboratory studies tend to be normal. A number of different peripheral and central mechanism have been proposed, which may not be mutually exclusive.
Peripheral: muscular involvement
The earliest efforts to understand FM assumed that reported pain was caused by abnormalities related to the muscle anatomy, physiological processes (eg, oxygen availability and depletion), or tension myalgia. Research suggests that the involvement of the peripheral pathology is, however, nonspecific, cannot account for the diverse symptoms, and is unlikely to be primary.5
Central: neurotransmitter dysregulation
Various neurochemical factors have been studied in patients with FM. These include dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and serotonin imbalance.4,6 However, no definitive neurochemical features have been consistently identified. What is most notable in studies that have examined various neuroendocrine substances in FM is the large intragroup variability observed in the substances tested. Thus, although persons with FM may differ statistically from those without FM, the large individual differences within patients with FM make it difficult to interpret the results.
1. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum. 1990;36:160-172.
2. Burckhardt CS, Goldenberg D, Crofford L, et al. Guidelines for the Management of Fibromyalgia Syndrome Pain in Adults and Children. APS Clinical Practice Guidelines Series, No 4. Glenview, IL: American Pain Society; 2005.
3. Turk DC, Okifuji A, Starz TW, Sinclair JD. Effects of type of symptom onset on psychological distress and disability in fibromyalgia syndrome patients. Pain. 1996;68:423-430.
4. Crofford LJ, Engleberg NC, Demitrack MA. Neurohormonal perturbations in fibromyalgia. Baillieres Clin Rheumatol. 1996;10:365-378.
5. Clauw DJ. Fibromyalgia: update on mechanisms and management. J Clin Rheumatol. 2007;13:102-109.
6. Wolfe F, Russell IJ, Vipraio G, et al. Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. J Rheumatol. 1997;24:555-559.
7. Adler GK, Geenen R. Hypothalamic-pituitary-adrenal and autonomic nervous system functioning in fibromyalgia. Rheum Dis Clin North Am. 2005;31:187-202.
8. Amital D, Fostick L, Polliack ML, et al. Posttraumatic stress disorder, tenderness, and fibromyalgia syndrome: are they different entities? J Psychosom Res. 2006;61:663-669.
9. Cohen H, Neumann L, Haiman Y, et al. Prevalence of post-traumatic stress disorder in fibromyalgia patients: overlapping syndromes or post-traumatic fibromyalgia syndrome? Semin Arthritis Rheum. 2002;32:38-50.
10. Bennett RM, Jones J, Turk DC, et al. An internet survey of 2,596 people with fibromyalgia. BMC Musculoskelet Disord. 2007;8:27.
11. Gupta A, Silman AJ. Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link. Arthritis ResTher. 2004;6:98-106.
12. Vierck CJ Jr. Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia). Pain. 2006;124:242-263.
13. Kosek E, Ekholm J, Hansson P. Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms. Pain. 1996;68:375-383.
14. Rollman GB, Lautenbacher S. Hypervigilance effects in fibromyalgia: pain experience and pain perception. In: Vaeroy H, Merskey H, eds. Progress in Fibromyalgia and Myofascial Pain. New York: Elsevier; 1993:89-112.
15. McDermid AJ, Rollman GB, McCain GA. Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification. Pain. 1996;66:133-144.
16. Buskila D, Sarzi-Puttini P, Albin JN. The genetics of fibromyalgia syndrome. Pharmacogenomics. 2007;8:67-74.
17. Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol. 2006;2:90-98.
18. Okifuji A, Turk DC. Fibromyalgia: search for mechanisms and effective treatments. In: Gatchel RJ, Turk DC, eds. Psychological Factors in Pain: Critical Perspectives. New York: Guilford; 1999:227-246.
19. Hudson JI, Pope HG Jr. The relationship between fibromyalgia and major depressive disorder. Rheum Dis Clin North Am. 1996;22:285-303.
20. Arnold LM, Hudson JI, Hess EV, et al. Family study of fibromyalgia. Arthritis Rheum. 2004;50:944-952.
21. Arnold LM, Hudson JI, Keck PE, et al. Comorbidity of fibromyalgia and psychiatric disorders. J Clin Psychiatry. 2006;67:1219-1225.
22. Goldenberg DL. Fibromyalgia syndrome a decade later: what have we learned? Arch Intern Med. 1999;159:777-785.
23. Berger A, Dukes E, Martin S, et al. Characteristics and healthcare costs of patients with fibromyalgia syndrome. Int J Clin Pract. 2007;61:1498-1508.
24. Wolfe F, Ross K, Anderson J, et al. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995;38:19-28.
25. White KP, Nielson WR, Harth M, et al. Chronic widespread musculoskeletal pain with or without fibromyalgia: psychological distress in a representative community adult sample. J Rheumatol. 2002;29:588-594.
26. Greenwood KA, Thurston R, Rumble M, et al. Anger and persistent pain: current status and future directions. Pain. 2003;103:1-5.
27. Amir M, Neumann L, Bor O, et al. Coping styles, anger, social support, and suicide risk of women with fibromyalgia syndrome. J Musculoskel Pain. 2000;8:7-20.
28. Sayar K, Gulec H, Topbas M. Alexthymia and anger in patients with fibromyalgia. Clin Rheumatol. 2004;23:441-448.
29. Fordyce W. Behavioral Methods for Chronic Pain and Illness. St Louis: Mosby; 1976.
30. Turk DC, Okifuji A. Perception of traumatic onset, compensation status, and physical findings: impact on pain severity, emotional distress, and disability in chronic pain patients. J Behav Med. 1996;9:435-453.
31. Jensen MP, Turner JA, Romano JM, Karoly P. Coping with chronic pain: a critical review of the literature. Pain. 1991;47:249-283.
32. Turk DC, Okifuji A. Psychological factors in chronic pain: evolution and revolutions. J Consult Clin Psychol. 2002;70:678-690.
33. Flor H, Turk DC. Chronic back pain and rheumatoid arthritis: predicting pain and disability from cognitive variables. J Behav Med. 1988;11:251-265.
34. Jensen MP, Turner JA, Romano JM, Lawler BK. Relationship of pain-specific beliefs to chronic pain adjustment. Pain. 1994;57:301-309.
35. Tota-Faucette ME, Gil KM, Williams DA, et al. Predictors of response to pain management treatment: the role of family environment and changes in cognitive processes. Clin J Pain. 1993;9:115-123.
36. Morley S, Eccleston C, Williams A. Systematic review and meta-analysis of randomized controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache. Pain. 1999;80:1-13.
37. Buckelew SP, Murray SE, Hewett JE, et al. Self-efficacy, pain, and physical activity among fibromyalgia subjects. Arthritis Care Res. 1995;8:43-50.
38. Arnold LM, Keck PE Jr, Welge JA. Antidepressant treatment of fibromyalgia: a meta-analysis and review. Psychosmatics. 2000;41: 104-113.
39. O’Malley PG, Balden E, Tomkins G, et al. Treatment of fibromyalgia with antidepressants: a meta-analysis. J Gen Internal Med. 2000;15: 659-666.
40. Carette S, Bell MJ, Reynolds WJ, et al. Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia: a randomized, double-blind clinical trial. Arthritis Rheum. 1994;37:32-40.
41. Burckhardt CS. Non-pharmacological treatment of fibromyalgia syndrome. J Funct Syndr. 2001;1:103-115.
42. Burckhardt CS. Nonpharmacologic management strategies in fibromyalgia. Rheum Dis Clin North Am. 2002;28:291-304.
43. Offenbacher M, Cieza A, Brokow T, et al. Are the contents of treatment outcomes in fibromyalgia trials represented in the international classification of functioning, disability, and health? Clin J Pain. 2007; 23:691-701.
44. Sim J, Adams N. Systematic review of randomized controlled trials of nonpharmacological interventions for fibromyalgia. Clin J Pain. 2002; 18:324-336.
45. Rossy LA, Buckelew SP, Dorr N, et al. A meta-analysis of fibromyalgia treatment interventions. Ann Behav Med. 1999;21:180-191.
46. Deutsche Interdisziplinäre Vereinigung für Schmerztherapie (DIVS). Interdisziplinaere Leilinie zur “Definition, Pathophysiologie, Diagnose und Therapie der Fibromyalgie. [German Association of Pain Therapy. Interdisciplinary guideline on the “Definition, pathophysiology, diagnosis and therapy of fibromyalgia.”] http://www.uni-duesseldorf.de/AWMF/ll/041-004.htm. Revised July 2008.
47. Karjalainen K, Malmivaara A, van Tulder M, et al. Multidisciplinary rehabilitation for fibromyalgia and musculoskeletal pain in working age adults. Cochrane Database Syst Rev. 2000;(3):CD001984.
48. Carville SF,Arendt-Nielsen S, Bliddal H, et al. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008;67:536-541.
49. Turk DC, Okifuji A, Sinclair JD, Starz TW. Pain, disability, and physical functioning in subgroups of patients with fibromyalgia. J Rheum. 1996;23:1255-1262.
50. Wilson HD, Robinson JP,Turk DC.Toward the identification of symptom patterns in people with fibromyalgia. Arthritis Care Res. In press.
51. Flor H, Birbaumer N, Turk DC. The psychobiology of chronic pain. Adv Behav Res Ther. 1990;12:47-84. 52. Turk DC, Monarch ES. Biopsychosocial perspective on pain. In:Turk DC, Gatchel RJ, eds, Psychological Approaches to Pain Management: A Practitioner’s Handbook. 2nd ed. New York: Guilford Press; 2002: 3-39.
Evidence-Based References
Burckhardt CS, Goldenberg D, Crofford L, et al. Guidelines for the Management of Fibromyalgia Syndrome Pain in Adults and Children. APS Clinical Practice Guidelines Series, No 4. Glenview, IL: American Pain Society; 2005.
Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum. 1990;36:160-172.
