Zusammenfassung
Ziel
Die Erstellung eines ersten systematischen Reviews zur Ätiopathogenese und Pathophysiologie des Fibromyalgiesyndroms (FMS) und chronischer Schmerzen in mehreren Körperregionen (engl. „chronic widespread pain“, CWP).
Methodik
Eine interdisziplinäre Leitlinie wurde in Kooperation von 10 medizinischen bzw. psychologischen Fachgesellschaften und 2 Patientenselbsthilfeorganisationen erstellt. Eine Literatursuche über alle Übersichtsarbeiten zur Ätiopathogenese und Pathophysiologie des FMS und CWP wurde unter Benutzung der Cochrane Collaboration Reviews (1993–12/2006), Medline (1980–2006), PsychInfo (1966–12/2006) und Scopus (1980–12/2006) durchgeführt. Für die Vergabe von Evidenzklassen wurde das System des Oxford Centre for Evidence-Based Medicine verwendet. Ein Konsens über die Evidenzklassen erfolgte in einem mehrstufigen nominalen Gruppenprozess.
Ergebnisse
Das FMS tritt gehäuft in Familien auf. Physische und psychische Stressoren am Arbeitsplatz sind Risikofaktoren für die Entwicklung von CWP und FMS. Affektive Störungen sind Risikofaktoren für die Entwicklung und Aufrechterhaltung eines FMS. Operante Lernmechanismen und Sensitivierung sind Risikofaktoren für die Chronifizierung eines FMS (Evidenzgrad 2b). Verschiedene Faktoren sind mit der Pathophysiologie des FMS assoziiert, ohne dass die Ursache-Wirkungs-Relation geklärt ist. Dazu gehören Störungen der zentralen Schmerzverarbeitung, eine Hyporeaktivität der Hypothalamus-Hypophysen-Nebennierenachse, eine Störung des Wachstumhormonsystems, erhöhte systemische proinflammatorische und verminderte antiinflammatorische Zytokinprofile, Veränderungen des dopaminergen und serotonergen Systems.
Schlussfolgerung
Das FMS ist eine Endstrecke verschiedener ätiopathogenetischer Faktoren und pathophysiologischer Mechanismen.
Abstract
Objective
To write a systematic review on the etiology and pathophysiology of the fibromyalgia syndrome (FMS) and of chronic widespread pain (CWP).
Methods
An interdisciplinary level-3 guideline (i.e. systematic literature search and assessment, logic analysis, formal consensus procedure) for the diagnosis and therapy of FMS was created in cooperation with 10 medical and psychological societies and 2 patient self-help organizations. A literature search was performed covering all available review articles on the etiology and pathophysiology of FMS and CWP using the Cochrane Collaboration Reviews (1993–12/2006), Medline (1980–2006), PsychInfo (1966–12/2006), and Scopus (1980–12/2006). For the assignment of evidence classes the system of the Oxford Centre for Evidence-Based Medicine was applied. Consensus was achieved by a multi-step nominal group procedure.
Results
FMS aggregates in families (evidence level 2c). Physical and psychological stress at the workplace are risk factors for the development of CWP and FMS. Affective disorders are risk factors for the development and maintenance of FMS. Operant learning mechanisms and sensitization are risk factors for the chronification of FMS (evidence levels 2b). Several factors are associated with the pathophysiology of FMS, but the causal relationship is unclear. This includes alterations of central pain pathways, hyporeactivity of the hypothalamus-pituitary-adrenal axis, increased systemic pro-inflammatory and reduced anti-inflammatory cytokine profiles and disturbances in the dopaminergic and serotonergic systems.
Conclusions
FMS is the common final product of various etiological factors and pathophysiological mechanisms.
Literatur
Adler GK, Kinsley BT, Hurwitz S et al. (1999) Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome. Am J Med 106: 534–543
Akkuş S, Delibaş N, Tamer MN (2000) Do sex hormones play a role in fibromyalgia? Rheumatology (Oxford) 39: 1161–1163
Al-Allaf AW, Dunbar KL, Hallum NS et al. (2002) A case-control study examining the role of physical trauma in the onset of fibromyalgia syndrome. Rheumatology (Oxford) 41: 450–453
Alanoğlu E, Ulaş UH, Özdağ F et al. (2005) Auditory event-related brain potentials in fibromyalgia syndrome. Rheumatol Int 25: 345–349
Alnıgeniş MN, Barland P (2001) Fibromyalgia syndrome and serotonin. Clin Exp Rheumatol 19: 205–210
Amel Kashipaz MR, Swinden D, Todd I et al. (2003) Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells. Clin Exp Immunol 132: 360–365
Anderberg UM, Uvnas-Moberg K (2000) Plasma oxytocin levels in female fibromyalgia syndrome patients. Z Rheumatol 59: 373–379
Anders C, Sprott H, Scholle HC (2001) Surface EMG of the lumbar part of the erector trunci muscle in patients with fibromyalgia. Clin Exp Rheumatol 19: 453–455
Ang DC, Peloso PM, Woolson RF et al. (2006) Predictors of incident chronic widespread pain among veterans following the first Gulf War. Clin J Pain 22: 554–563
Arnold LM, Hudson JI, Hess EV et al. (2004) Family study of fibromyalgia. Arthritis Rheum 50: 944–952
Arnold LM, Hudson JI, Keck PE et al. (2006) Comorbidity of fibromyalgia and psychiatric disorders. J Clin Psychiatry 67: 1219–1225
Ataoğlu S, Özçetin A, Yildiz O et al. (2003) Evaluation of dexamethasone suppression test in fibromyalgia patients with or without depression. Swiss Med Wkly 133: 241–244
Bagge E, Bengtsson BA, Carlsson L et al. (1998) Low growth hormone secretion in patients with fibromyalgia – a preliminary report on 10 patients and 10 controls. J Rheumatol 25: 145–148
Banic B, Petersen-Felix S, Andersen OK et al. (2004) Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia. Pain 107: 7–15
Bartels EM, Danneskiold-Samsoe B (1986) Histological abnormalities in muscle from patients with certain types of fibrositis. Lancet 1: 755–757
Bengtsson A, Henriksson KG, Larsson J (1986) Muscle biopsy in primary fibromyalgia. Light-microscopical and histochemical findings. Scand J Rheumatol 15: 1–6
Bengtsson A, Henriksson KG, Larsson J (1986) Reduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgia. Arthritis Rheum 29: 817–821
Bennett RM, Clark SR, Campbell SM et al. (1992) Low levels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain. Arthritis Rheum 35: 1113–1116
Bennett RM, Clark SR, Goldberg L et al. (1989) Aerobic fitness in patients with fibrositis. A controlled study of respiratory gas exchange and 133xenon clearance from exercising muscle. Arthritis Rheum 32: 454–460
Bennett RM, Cook DM, Clark SR et al. (1997) Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia. J Rheumatol 24: 1384–1389
Berg AM, Naides SJ, Simms RW (1993) Established fibromyalgia syndrome and parvovirus B19 infection. J Rheumatol 20: 1941–1943
Bonafede RP, Downey DC, Bennett RM (1995) An association of fibromyalgia with primary Sjogren’s syndrome: a prospective study of 72 patients. J Rheumatol 22: 133–136
Bondy B, Spaeth M, Offenbaecher M et al. (1999) The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia. Neurobiol Dis 6: 433–439
Bou-Holaigah I, Calkins H, Flynn JA et al. (1997) Provocation of hypotension and pain during upright tilt table testing in adults with fibromyalgia. Clin Exp Rheumatol 15: 239–246
Brown SL, Pennello G, Berg WA et al. (2001) Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women. J Rheumatol 28: 996–1003
Buchwald D, Goldenberg DL, Sullivan JL et al. (1987) The chronic, active Epstein-Barr virus infection syndrome and primary fibromyalgia. Arthritis Rheum 30: 1132–1136
Buchwald D, Umali J, Stene M (1996) Insulin-like growth factor-I (somatomedin C) levels in chronic fatigue syndrome and fibromyalgia. J Rheumatol 23: 739–742
Burda CD, Cox FR, Osborne P (1986) Histocompatability antigens in the fibrositis (fibromyalgia) syndrome. Clin Exp Rheumatol 4: 355–358
Buskila D, Cohen H, Neumann L et al. (2004) An association between fibromyalgia and the dopamine D4 receptor exon III repeat polymorphism and relationship to novelty seeking personality traits. Mol Psychiatry 9: 730–731
Buskila D, Neumann L (1997) Fibromyalgia syndrome (FM) and nonarticular tenderness in relatives of patients with FM. J Rheumatol 24: 941–944
Buskila D, Neumann L, Hazanov I et al. (1996) Familial aggregation in the fibromyalgia syndrome. Semin Arthritis Rheum 26: 605–611
Buskila D, Neumann L, Vaisberg G et al. (1997) Increased rates of fibromyalgia following cervical spine injury. A controlled study of 161 cases of traumatic injury. Arthritis Rheum 40: 446–452
Buskila D, Shnaider A, Neumann L et al. (1997) Fibromyalgia in hepatitis C virus infection. Another infectious disease relationship. Arch Intern Med 157: 2497–2500
Cairns V, Godwin J (2005) Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms. Int J Epidemiol 34: 1340–1345
Çaliş M, Gökce C, Ateş F et al. (2004) Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome. J Endocrinol Invest 27: 42–46
Campbell SM, Clark S, Tindall EA et al. (1983) Clinical characteristics of fibrositis. I. A „blinded,“ controlled study of symptoms and tender points. Arthritis Rheum 26: 817–824
Carette S, Lefrancois L (1988) Fibrositis and primary hypothyroidism. J Rheumatol 15: 1418–1421
Carrillo-de-la-Pena MT, Vallet M, Perez MI et al. (2006) Intensity dependence of auditory-evoked cortical potentials in fibromyalgia patients: a test of the generalized hypervigilance hypothesis. J Pain 7: 480–487
Catley D, Kaell AT, Kirschbaum C et al. (2000) A naturalistic evaluation of cortisol secretion in persons with fibromyalgia and rheumatoid arthritis. Arthritis Care Res 13: 51–61
Cohen H, Buskila D, Neumann L et al. (2002) Confirmation of an association between fibromyalgia and serotonin transporter promoter region (5- HTTLPR) polymorphism and relationship to anxiety-related personality traits. Arthritis Rheum 46: 845–847
Cohen H, Neumann L, Alhosshle A et al. (2001) Abnormal sympathovagal balance in men with fibromyalgia. J Rheumatol 28: 581–589
Cohen H, Neumann L, Haiman Y et al. (2002) Prevalence of post-traumatic stress disorder in fibromyalgia patients: overlapping syndromes or post-traumatic fibromyalgia syndrome? Semin Arthritis Rheum 32: 38–50
Cohen H, Neumann L, Kotler M et al. (2001) Autonomic nervous system derangement in fibromyalgia syndrome and related disorders. Isr Med Assoc J 3: 755–760
Cohen H, Neumann L, Shore M et al. (2000) Autonomic dysfunction in patients with fibromyalgia: application of power spectral analysis of heart rate variability. Semin Arthritis Rheum 29: 217–227
Cook DB, Lange G, Ciccone DS et al. (2004) Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol 31: 364–378
Crofford LJ (1998) The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome. Z Rheumatol 57 [suppl 2]: 67–71
Crofford LJ, Pillemer SR, Kalogeras KT et al. (1994) Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia. Arthritis Rheum 37: 1583–1592
Crofford LJ, Young EA, Engleberg NC et al. (2004) Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome. Brain Behav Immun 18: 314–325
Crombez G, Eccleston C, van den Broeck A et al. (2004) Hypervigilance to pain in fibromyalgia: the mediating role of pain intensity and catastrophic thinking about pain. Clin J Pain 20: 98–102
Cruz BA, Catalan-Soares B, Proietti F (2006) Higher prevalence of fibromyalgia in patients infected with human T cell lymphotropic virus type I. J Rheumatol 33: 2300–2303
Dalhstrom L, Widmark G, Carlsson SG (1997) Cognitive-behavioral profiles among different categories of orofacial pain patients: diagnostic and treatment implications. Eur J Oral Sci 105: 377–383
De Stefano R, Selvi E, Villanova M et al. (2000) Image analysis quantification of substance P immunoreactivity in the trapezius muscle of patients with fibromyalgia and myofascial pain syndrome. J Rheumatol 27: 2906–2910
Denko CW, Malemud CJ (2005) Serum growth hormone and insulin but not insulin-like growth factor-1 levels are elevated in patients with fibromyalgia syndrome. Rheumatol Int 25: 146–151
Diatchenko L, Slade GD, Nackley AG et al. (2005) Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 14: 135–143
Dinerman H, Steere AC (1992) Lyme disease associated with fibromyalgia. Ann Intern Med 117: 281–285
Dohrenbusch R (2001) Sind Fibromyalgiepatienten „hypervigiliant“. Schmerz 15: 38–47
Dohrenbusch R, Gruterich M, Genth E (1996) Fibromyalgie und Sjogren-Syndrom – klinische und methodische Aspekte. Z Rheumatol 55: 19–27
Drewes AM, Andreasen A, Schroder HD et al. (1993) Pathology of skeletal muscle in fibromyalgia: a histo-immuno-chemical and ultrastructural study. Br J Rheumatol 32: 479–483
Elam M, Johansson G, Wallin BG (1992) Do patients with primary fibromyalgia have an altered muscle sympathetic nerve activity? Pain 48: 371–375
Elert JE, Rantapaa Dahlqvist SB, Henriksson-Larsen K et al. (1989) Increased EMG activity during short pauses in patients with primary fibromyalgia. Scand J Rheumatol 18: 321–323
Ernberg M, Voog U, Alstergren P et al. (2000) Plasma and serum serotonin levels and their relationship to orofacial pain and anxiety in fibromyalgia. J Orofac Pain 14: 37–46
Forseth KO, Husby G, Gran JT et al. (1999) Prognostic factors for the development of fibromyalgia in women with self-reported musculoskeletal pain. A prospective study. J Rheumatol 26: 2458–2467
Frank B, Niesler B, Bondy B et al. (2004) Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients. Clin Rheumatol 23: 338–344
Fryzek JP, Holmich L, McLaughlin JK et al. (2007) A nationwide study of connective tissue disease and other rheumatic conditions among Danish women with long-term cosmetic breast implantation. Ann Epidemiol 17: 374–379
Furlan R, Colombo S, Perego F et al. (2005) Abnormalities of cardiovascular neural control and reduced orthostatic tolerance in patients with primary fibromyalgia. J Rheumatol 32: 1787–1793
Fye KH, Whiting-O’Keefe QE, Lennette ET et al. (1988) Absence of abnormal Epstein-Barr virus serologic findings in patients with fibrositis. Arthritis Rheum 31: 1455–1456
Giesecke T, Gracely RH, Williams DA et al. (2005) The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. Arthritis Rheum 52: 1577–1584
Giesecke T, Williams DA, Harris RE et al. (2003) Subgrouping of fibromyalgia patients on the basis of pressure-pain thresholds and psychological factors. Arthritis Rheum 48: 2916–2922
Glass JM, Lyden AK, Petzke F et al. (2004) The effect of brief exercise cessation on pain, fatigue, and mood symptom development in healthy, fit individuals. J Psychosom Res 57: 391–398
Goulding C, O’Connell P, Murray FE (2001) Prevalence of fibromyalgia, anxiety and depression in chronic hepatitis C virus infection: relationship to RT-PCR status and mode of acquisition. Eur J Gastroenterol Hepatol 13: 507–511
Gracely RH, Geisser ME, Giesecke T et al. (2004) Pain catastrophizing and neural responses to pain among persons with fibromyalgia. Brain 127: 835–843
Gracely RH, Grant MA, Giesecke T (2003) Evoked pain measures in fibromyalgia. Best Pract Res Clin Rheumatol 17: 593–609
Gracely RH, Petzke F, Wolf JM et al. (2002) Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 46: 1333–1343
Graven-Nielsen T, Svensson P, Arendt-Nielsen L (1997) Effects of experimental muscle pain on muscle activity and co-ordination during static and dynamic motor function. Electroencephalogr Clin Neurophysiol 105: 156–164
Griep EN, Boersma JW, de Kloet ER (1993) Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome. J Rheumatol 20: 469–474
Griep EN, Boersma JW, de Kloet ER (1994) Pituitary release of growth hormone and prolactin in the primary fibromyalgia syndrome. J Rheumatol 21: 2125–2130
Griep EN, Boersma JW, Lentjes EG et al. (1998) Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain. J Rheumatol 25: 1374–1381
Gronemann ST, Ribel-Madsen S, Bartels EM et al. (2004) Collagen and muscle pathology in fibromyalgia patients. Rheumatology (Oxford) 43: 27–31
Gür A, Cevik R, Nas K et al. (2004) Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones. Arthritis Res Ther 6: 232–238
Gür A, Karakoç M, Erdoğan S et al. (2002) Regional cerebral blood flow and cytokines in young females with fibromyalgia. Clin Exp Rheumatol 20: 753–760
Gür A, Karakoç M, Nas K et al. (2002) Cytokines and depression in cases with fibromyalgia. J Rheumatol 29: 358–361
Gürsel Y, Ergin S, Ulus Y et al. (2001) Hormonal responses to exercise stress test in patients with fibromyalgia syndrome. Clin Rheumatol 20: 401–405
Gürsoy S (2002) Absence of association of the serotonin transporter gene polymorphism with the mentally healthy subset of fibromyalgia patients. Clin Rheumatol 21: 194–197
Gürsoy S, Erdal E, Herken H et al. (2001) Association of T102C polymorphism of the 5-HT2A receptor gene with psychiatric status in fibromyalgia syndrome. Rheumatol Int 21: 58–61
Gürsoy S, Erdal E, Herken H et al. (2003) Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome. Rheumatol Int 23: 104–107
Hader N, Rimon D, Kinarty A et al. (1991) Altered interleukin-2 secretion in patients with primary fibromyalgia syndrome. Arthritis Rheum 34: 866–872
Harkness EF, Macfarlane GJ, Nahit E et al. (2004) Mechanical injury and psychosocial factors in the work place predict the onset of widespread body pain: a two-year prospective study among cohorts of newly employed workers. Arthritis Rheum 50: 1655–1664
Häuser W, Bernardy K, Arnold B (2006) Das Fibromyalgiesyndrom – eine somatoforme (Schmerz)störung? Schmerz 20: 128–139
Häuser W, Zimmer C, Felde E et al. (2008) What are the key symptoms of fibromyalgia syndrome? Results of a survey of the German Fibromyalgia Association. Schmerz, in press
Heffez DS, Ross RE, Shade-Zeldow Y et al. (2004) Clinical evidence for cervical myelopathy due to Chiari malformation and spinal stenosis in a non-randomized group of patients with the diagnosis of fibromyalgia. Eur Spine J 13: 516–523
Holmich LR, Kjoller K, Fryzek JP et al. (2003) Self-reported diseases and symptoms by rupture status among unselected Danish women with cosmetic silicone breast implants discussion. Plast Reconstr Surg 111: 723–734
Horven S, Stiles TC, Holst A et al. (1992) HLA antigens in primary fibromyalgia syndrome. J Rheumatol 19: 1269–1270
Imbierowicz K, Egle UT (2003) Childhood adversities in patients with fibromyalgia and somatoform pain disorder. Eur J Pain 7: 113–119
Jacobsen S, Bartels EM, Danneskiold-Samsoe B (1991) Single cell morphology of muscle in patients with chronic muscle pain. Scand J Rheumatol 20: 336–343
Jacobsen S, Jensen KE, Thomsen C et al. (1992) 31P magnetic resonance spectroscopy of skeletal muscle in patients with fibromyalgia. J Rheumatol 19: 1600–1603
Jacobsen S, Main K, Danneskiold-Samsoe B et al. (1995) A controlled study on serum insulin-like growth factor-I and urinary excretion of growth hormone in fibromyalgia. J Rheumatol 22: 1138–1140
Jubrias SA, Bennett RM, Klug GA (1994) Increased incidence of a resonance in the phosphodiester region of 31P nuclear magnetic resonance spectra in the skeletal muscle of fibromyalgia patients. Arthritis Rheum 37: 801–807
Julien N, Goffaux P, Arsenault P et al. (2005) Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain 114: 295–302
Kalyan-Raman UP, Kalyan-Raman K, Yunus MB et al. (1984) Muscle pathology in primary fibromyalgia syndrome: a light microscopic, histochemical and ultrastructural study. J Rheumatol 11: 808–813
Kato K, Sullivan PF, Evengard B et al. (2006) Importance of genetic influences on chronic widespread pain. Arthritis Rheum 54: 1682–1686
Kelemen J, Lang E, Balint G et al. (1998) Orthostatic sympathetic derangement of baroreflex in patients with fibromyalgia. J Rheumatol 25: 823–825
Kirnap M, Çolak R, Eser C et al. (2001) A comparison between low-dose (1 microg), standard-dose (250 microg) ACTH stimulation tests and insulin tolerance test in the evaluation of hypothalamo-pituitary-adrenal axis in primary fibromyalgia syndrome. Clin Endocrinol (Oxf) 55: 455–459
Kivimäki M, Leino-Arjas P, Virtanen M et al. (2004) Work stress and incidence of newly diagnosed fibromyalgia: prospective cohort study. J Psychosom Res 57: 417–422
Kjoller K, Friis S, Mellemkjaer L et al. (2001) Connective tissue disease and other rheumatic conditions following cosmetic breast implantation in Denmark. Arch Intern Med 161: 973–979
Klerman EB, Goldenberg DL, Brown EN et al. (2001) Circadian rhythms of women with fibromyalgia. J Clin Endocrinol Metab 86: 1034–1039
Korszun A, Sackett-Lundeen L, Papadopoulos E et al. (1999) Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol 26: 2675–2680
Kozanoğlu E, Canataroğlu A, Abayli B et al. (2003) Fibromyalgia syndrome in patients with hepatitis C infection. Rheumatol Int 23: 248–251
Kuchinad A, Schweinhardt P, Seminowicz DA et al. (2007) Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J Neurosci 27: 4004–4007
Kwiatek R, Barnden L, Tedman R et al. (2000) Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami. Arthritis Rheum 43: 2823–2833
Labus JS, Keefe FJ, Jensen MP (2003) Self-reports of pain intensity and direct observations of pain behavior: when are they correlated? Pain 102: 109–124
Lai S, Goldman JA, Child AH et al. (2000) Fibromyalgia, hypermobility, and breast implants. J Rheumatol 27: 2237–2241
Larson AA, Giovengo SL, Russell IJ et al. (2000) 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 87: 201–211
Lentjes EG, Griep EN, Boersma JW et al. (1997) Glucocorticoid receptors, fibromyalgia and low back pain. Psychoneuroendocrinology 22: 603–614
Lindh M, Johansson G, Hedberg M et al. (1995) Muscle fiber characteristics, capillaries and enzymes in patients with fibromyalgia and controls. Scand J Rheumatol 24: 34–37
Lipowski ZJ (1988) Somatization: the concept and its clinical application. Am J Psychiatry 145: 1358–1368
Lipworth L, Tarone RE, McLaughlin JK (2004) Breast implants and fibromyalgia: a review of the epidemiologic evidence. Ann Plast Surg 52: 284–287
Lorenz J (1998) Hyperalgesia or hypervigilance? An evoked potential approach to the study of fibromyalgia syndrome. Z Rheumatol 57 [suppl 2]: 19–22
Lund E, Kendall SA, Janerot-Sjoberg B et al. (2003) Muscle metabolism in fibromyalgia studied by P-31 magnetic resonance spectroscopy during aerobic and anaerobic exercise. Scand J Rheumatol 32: 138–145
Lund N, Bengtsson A, Thorborg P (1986) Muscle tissue oxygen pressure in primary fibromyalgia. Scand J Rheumatol 15: 165–173
Macfarlane TV, Blinkhorn A, Worthington HV et al. (2002) Sex hormonal factors and chronic widespread pain: a population study among women. Rheumatology (Oxford) 41: 454–457
Maes M, Libbrecht I, van Hunsel F et al. (1999) The immune-inflammatory pathophysiology of fibromyalgia: increased serum soluble gp130, the common signal transducer protein of various neurotrophic cytokines. Psychoneuroendocrinology 24: 371–383
Maes M, Lin A, Bonaccorso S et al. (1998) Increased 24-hour urinary cortisol excretion in patients with post-traumatic stress disorder and patients with major depression, but not in patients with fibromyalgia. Acta Psychiatr Scand 98: 328–335
Maes M, Verkerk R, Delmeire L et al. (2000) Serotonergic markers and lowered plasma branched-chain-amino acid concentrations in fibromyalgia. Psychiatry Res 97: 11–20
Magni G, Moreschi C, Rigatti-Luchini S et al. (1994) Prospective study on the relationship between depressive symptoms and chronic musculoskeletal pain. Pain 56: 289–297
Maixner W (2004) Hyperalgesia: molecular mechanisms and clinical implications. In: Brune K, Handwerker HO (eds) Progress in pain research and management, vol 30. IASP Press, Seattle, pp 373–386
Maliszewski AM, Goldenberg DL, Hurwitz S et al. (2002) Regulation of the renin-angiotensin-aldosterone system in fibromyalgia. J Rheumatol 29: 1482–1487
Malt EA, Olafsson S, Aakvaag A et al. (2003) Altered dopamine D2 receptor function in fibromyalgia patients: a neuroendocrine study with buspirone in women with fibromyalgia compared to female population based controls. J Affect Disord 75: 77–82
Martinez-Lavin M, Hermosillo AG, Mendoza C et al. (1997) Orthostatic sympathetic derangement in subjects with fibromyalgia. J Rheumatol 24: 714–718
Martinez-Lavin M, Hermosillo AG, Rosas M et al. (1998) Circadian studies of autonomic nervous balance in patients with fibromyalgia: a heart rate variability analysis. Arthritis Rheum 41: 1966–1971
McBeth J, Chiu YH, Silman AJ et al. (2005) Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents. Arthritis Res Ther 7: 992-1000
McBeth J, Harkness EF, Silman AJ et al. (2003) The role of workplace low-level mechanical trauma, posture and environment in the onset of chronic widespread pain. Rheumatology (Oxford) 42: 1486–1494
McBeth J, Macfarlane GJ, Hunt IM et al. (2001) Risk factors for persistent chronic widespread pain: a community-based study. Rheumatology (Oxford) 40: 95–101
McBeth J, Macfarlane GJ, Silman AJ (2002) Does chronic pain predict future psychological distress? Pain 96: 239–245
McBeth J, Morris S, Benjamin S et al. (2001) Associations between adverse events in childhood and chronic widespread pain in adulthood: are they explained by differential recall? J Rheumatol 28: 2305–2309
McCain GA, Tilbe KS (1989) Diurnal hormone variation in fibromyalgia syndrome: a comparison with rheumatoid arthritis. J Rheumatol 19 [suppl]: 154–157
McCall-Hosenfeld JS, Goldenberg DL, Hurwitz S et al. (2003) Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia. J Rheumatol 30: 809–814
McDermid AJ, Rollman GB, McCain GA (1996) Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification. Pain 66: 133–144
McLean SA, Williams DA, Clauw DJ (2005) Fibromyalgia after motor vehicle collision: evidence and implications. Traffic Inj Prev 6: 97–104
McLean SA, Williams DA, Harris RE et al. (2005) Momentary relationship between cortisol secretion and symptoms in patients with fibromyalgia. Arthritis Rheum 52: 3660–3669
McLean SA, Williams DA, Stein PK et al. (2006) Cerebrospinal fluid corticotropin-releasing factor concentration is associated with pain but not fatigue symptoms in patients with fibromyalgia. Neuropsychopharmacology 31: 2776–2782
Meadows J, Kraut M, Guarnieri M et al. (2000) Asymptomatic Chiari type I malformations identified on magnetic resonance imaging. J Neurosurg 92: 920–926
Mease P (2005) Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol 75 [suppl]: 6–21
Moldofsky H (1982) Rheumatic pain modulation syndrome: the interrelationships between sleep, central nervous system serotonin, and pain. Adv Neurol 33: 51–7
Mountz JM, Bradley LA, Modell JG et al. (1995) 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 38: 926–938
Narvaez J, Nolla JM, Valverde-Garcia J (2005) Lack of association of fibromyalgia with hepatitis C virus infection. J Rheumatol 32: 1118–1121
Narvaez J, Nolla JM, Valverde J (2005) No serological evidence that fibromyalgia is linked with exposure to human parvovirus B19. Joint Bone Spine 72: 592–594
Nasralla M, Haier J, Nicolson GL (1999) Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Eur J Clin Microbiol Infect Dis 18: 859–865
Neeck G, Riedel W (1992) Thyroid function in patients with fibromyalgia syndrome. J Rheumatol 19: 1120–1122
Nyren O, Yin L, Josefsson S et al. (1998) Risk of connective tissue disease and related disorders among women with breast implants: a nation-wide retrospective cohort study in Sweden. BMJ 316: 417–422
Offenbaecher M, Bondy B, de Jonge S et al. (1999) Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region. Arthritis Rheum 42: 2482–2488
Ostensen M, Rugelsjoen A, Wigers SH (1997) The effect of reproductive events and alterations of sex hormone levels on the symptoms of fibromyalgia. Scand J Rheumatol 26: 355–360
Ostuni P, Botsios C, Sfriso P et al. (2002) Fibromyalgia in Italian patients with primary Sjogren’s syndrome. Joint Bone Spine 69: 51–57
Park JH, Phothimat P, Oates CT et al. (1998) Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia. Arthritis Rheum 41: 406–413
Pellegrino MJ, Waylonis GW, Sommer A (1989) Familial occurrence of primary fibromyalgia. Arch Phys Med Rehabil 70: 61–63
Pendarvis WT, Pillemer SR (2001) Widespread pain and Sjogren’s syndrome. J Rheumatol 28: 2657–2659
Peters ML, Vlaeyen JW, van Drunen C (2000) Do fibromyalgia patients display hypervigilance for innocuous somatosensory stimuli? Application of a body scanning reaction time paradigm. Pain 86: 283–292
Petzke F, Clauw DJ, Ambrose K et al. (2003) Increased pain sensitivity in fibromyalgia: effects of stimulus type and mode of presentation. Pain 105: 403–413
Pöyhiä R, Da Costa D, Fitzcharles MA (2001) Previous pain experience in women with fibromyalgia and inflammatory arthritis and nonpainful controls. J Rheumatol 28: 1888–1891
Qiao ZG, Vaeroy H, Morkrid L (1991) Electrodermal and microcirculatory activity in patients with fibromyalgia during baseline, acoustic stimulation and cold pressor tests. J Rheumatol 18: 1383–1389
Raj SR, Brouillard D, Simpson CS et al. (2000) Dysautonomia among patients with fibromyalgia: a noninvasive assessment. J Rheumatol 27: 2660–2665
Raphael KG, Chandler HK, Ciccone DS (2004) Is childhood abuse a risk factor for chronic pain in adulthood? Curr Pain Headache Rep 8: 99–110
Raphael KG, Janal MN, Nayak S (2004) Comorbidity of fibromyalgia and posttraumatic stress disorder symptoms in a community sample of women. Pain Med 5: 33–41
Raphael KG, Janal MN, Nayak S et al. (2004) Familial aggregation of depression in fibromyalgia: a community-based test of alternate hypotheses. Pain 110: 449–460
Raphael KG, Natelson BH, Janal MN et al. (2002) A community-based survey of fibromyalgia-like pain complaints following the World Trade Center terrorist attacks. Pain 100: 131–139
Reynolds WJ, Chiu B, Inman RD (1988) Plasma substance P levels in fibrositis. J Rheumatol 15: 1802–1803
Ribeiro LS, Proietti FA (2004) Interrelations between fibromyalgia, thyroid autoantibodies, and depression. J Rheumatol 31: 2036–2040
Riedel W, Layka H, Neeck G (1998) Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones. Z Rheumatol 57 [suppl 2]: 81–87
Rivera J, de Diego A, Trinchet M et al. (1997) Fibromyalgia-associated hepatitis C virus infection. Br J Rheumatol 36: 981–985
Russell IJ (1989) Neurohormonal aspects of fibromyalgia syndrome. Rheum Dis Clin North Am 15: 149–168
Russell IJ, Michalek JE, Vipraio GA et al. (1992) Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol 19: 104–109
Russell IJ, Michalek JE, Vipraio GA et al. (1989) Serum amino acids in fibrositis/fibromyalgia syndrome. J Rheumatol 19 [suppl]: 158–163
Russell IJ, Orr MD, Littman B et al. (1994) Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum 37: 1593–1601
Russell IJ, Vaeroy H, Javors M et al. (1992) Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum 35: 550–556
Salemi S, Rethage J, Wollina U et al. (2003) Detection of interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha in skin of patients with fibromyalgia. J Rheumatol 30: 146–150
Samborski W, Sobieska M, Pieta P et al. (2005) Normal profile of sex hormones in women with primary fibromyalgia. Ann Acad Med Stetin 51: 23–26
Samborski W, Stratz T, Schochat T et al. (1996) Biochemische Veränderungen bei der Fibromyalgie. Z Rheumatol 55: 168–173
Schochat T, Beckmann C (2003) Soziodemographie, Risikofaktoren und Reproduktionsanamnese bei Fibromyalgie. Ergebnisse einer bevolkerungsbezogenen Studie. Z Rheumatol 62: 46–59
Schwarz MJ, Offenbaecher M, Neumeister A et al. (2002) Evidence for an altered tryptophan metabolism in fibromyalgia. Neurobiol Dis 11: 434–442
Simms RW, Roy SH, Hrovat M et al. (1994) Lack of association between fibromyalgia syndrome and abnormalities in muscle energy metabolism. Arthritis Rheum 37: 794–800
Simms RW, Zerbini CA, Ferrante N et al. (1992) Fibromyalgia syndrome in patients infected with human immunodeficiency virus. The Boston City Hospital Clinical AIDS Team. Am J Med 92: 368–374
Sörensen J, Graven-Nielsen T, Henriksson KG et al. (1998) Hyperexcitability in fibromyalgia. J Rheumatol 25: 152–155
Sprott H, Bradley LA, Oh SJ et al. (1998) Immunohistochemical and molecular studies of serotonin, substance P, galanin, pituitary adenylyl cyclase-activating polypeptide, and secretoneurin in fibromyalgic muscle tissue. Arthritis Rheum 41: 1689–1694
Sprott H, Rzanny R, Reichenbach JR et al. (2000) 31P magnetic resonance spectroscopy in fibromyalgic muscle. Rheumatology (Oxford) 39: 1121–1125
Sprott H, Salemi S, Gay RE et al. (2004) Increased DNA fragmentation and ultrastructural changes in fibromyalgic muscle fibres. Ann Rheum Dis 63: 245–251
Staud R, Cannon RC, Mauderli AP et al. (2003) Temporal summation of pain from mechanical stimulation of muscle tissue in normal controls and subjects with fibromyalgia syndrome. Pain 102: 87–95
Staud R, Domingo M (2001) Evidence for abnormal pain processing in fibromyalgia syndrome. Pain Med 2: 208–215
Staud R, Vierck CJ, Cannon RL et al. (2001) Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain 91: 165–75
Stratz T, Samborski W, Hrycaj P et al. (1993) Die Serotoninkonzentration im Serum bei Patienten mit generalisierter Tendomyopathie (Fibromyalgie) und chronischer Polyarthritis. Med Klin (Munich) 88: 458–462
Stratz T, Varga B, Muller W (2003) Beeinflusst die Depressivitat den Behandlungseffekt von Tropisetron bei Fibromyalgiepatienten? Z Rheumatol 62: 42–45
Strobel ES, Krapf M, Suckfull M et al. (1997) Tissue oxygen measurement and 31P magnetic resonance spectroscopy in patients with muscle tension and fibromyalgia. Rheumatol Int 16: 175–180
Svebak S, Anjia R, Karstad SI (1993) Task-induced electromyographic activation in fibromyalgia subjects and controls. Scand J Rheumatol 22: 124–130
Thieme K, Spies C, Sinha P et al. (2005) Predictors of pain behaviors in fibromyalgia syndrome. Arthritis Rheum 53: 343–350
Thieme K, Turk DC (2006) Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients. Arthritis Res Ther 8: 9
Thieme K, Turk DC, Flor H (2004) Comorbid depression and anxiety in fibromyalgia syndrome: relationship to somatic and psychosocial variables. Psychosom Med 66: 837–844
Thieme K, Turk DC, Flor H (2008) Psychological characteristics of psychophysiologically defined subgroups of fibromyalgia syndrome patients. In press
Thimineur M, Kitaj M, Kravitz E et al. (2002) Functional abnormalities of the cervical cord and lower medulla and their effect on pain: observations in chronic pain patients with incidental mild Chiari I malformation and moderate to severe cervical cord compression. Clin J Pain 18: 171–179
Tishler M, Levy O, Maslakov I et al. (2006) Neck injury and fibromyalgia – are they really associated? J Rheumatol 33: 1183–1185
Torpy DJ, Papanicolaou DA, Lotsikas AJ et al. (2000) Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: a pilot study in fibromyalgia. Arthritis Rheum 43: 872–880
Turk DC, Okifuji A, Sinclair JD et al. (1998) Interdisciplinary treatment for fibromyalgia syndrome: clinical and statistical significance. Arthritis Care Res 11: 186–195
Turk DC, Okifuji A, Starz TW et al. (1996) Effects of type of symptom onset on psychological distress and disability in fibromyalgia syndrome patients. Pain 68: 423–430
Üçeyler N, Valenza R, Stock M et al. (2006) Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum 54: 2656–2664
Vaeroy H, Helle R, Forre O et al. (1988) Cerebrospinal fluid levels of beta-endorphin in patients with fibromyalgia (fibrositis syndrome). J Rheumatol 15: 1804–1806
Vaeroy H, Qiao ZG, Morkrid L et al. (1989) Altered sympathetic nervous system response in patients with fibromyalgia (fibrositis syndrome). J Rheumatol 16: 1460–1465
Van Denderen JC, Boersma JW, Zeinstra P et al. (1992) Physiological effects of exhaustive physical exercise in primary fibromyalgia syndrome (PFS): is PFS a disorder of neuroendocrine reactivity? Scand J Rheumatol 21: 35–37
Van Houdenhove B, Egle UT (2004) Fibromyalgia: a stress disorder? Piecing the biopsychosocial puzzle together. Psychother Psychosom 73: 267–275
Van Houdenhove B, Luyten P (2006) Stress, depression and fibromyalgia. Acta Neurol Belg 106: 149–156
Vestergaard-Poulsen P, Thomsen C, Sinkjaer T et al. (1992) Simultaneous electromyography and 31P nuclear magnetic resonance spectroscopy – with application to muscle fatigue. Electroencephalogr Clin Neurophysiol 85: 402–411
Vierck CJ Jr (2006) Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia). Pain 124: 242–263
Vierck CJ jr, Staud R, Price DD et al. (2001) The effect of maximal exercise on temporal summation of second pain (windup) in patients with fibromyalgia syndrome. J Pain 2: 334–344
Vlaeyen JW, Linton SJ (2000) Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of the art. Pain 85: 317–332
Wallace DJ, Linker-Israeli M, Hallegua D et al. (2001) Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study. Rheumatology (Oxford) 40: 743–749
Weir PT, Harlan GA, Nkoy FL et al. (2006) The incidence of fibromyalgia and its associated comorbidities: a population-based retrospective cohort study based on International Classification of Diseases, 9th revision codes. J Clin Rheumatol 12: 124–128
Werle E, Fischer HP, Muller A et al. (2001) Antibodies against serotonin have no diagnostic relevance in patients with fibromyalgia syndrome. J Rheumatol 28: 595–600
Wik G, Fischer H, Bragee B et al. (1999) Functional anatomy of hypnotic analgesia: a PET study of patients with fibromyalgia. Eur J Pain 3: 7–12
Wik G, Fischer H, Finer B et al. (2006) Retrospenial cortical deactivation during painful stimulation of fibromyalgic patients. Int J Neurosci 116: 1–8
Williams DA, Brown SC, Clauw DJ et al. (2003) Self-reported symptoms before and after September 11 in patients with fibromyalgia. JAMA 289: 1637–1638
Wingenfeld K, Wagner D, Schmidt I et al. (2007) The low-dose dexamethasone suppression test in fibromyalgia. J Psychosom Res 62: 85–91
Wittrup IH, Christensen LS, Jensen B et al. (2000) Search for Borna disease virus in Danish fibromyalgia patients. Scand J Rheumatol 29: 387–390
Wittrup IH, Jensen B, Bliddal H et al. (2001) Comparison of viral antibodies in 2 groups of patients with fibromyalgia. J Rheumatol 28: 601–603
Wolfe F, Anderson J (1999) Silicone filled breast implants and the risk of fibromyalgia and rheumatoid arthritis. J Rheumatol 26: 2025–2028
Wolfe F, Michaud K (2004) Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize ra patients with fibromyalgia. J Rheumatol 31: 695–700
Wolfe F, Russell IJ, Vipraio G et al. (1997) Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. J Rheumatol 24: 555–559
Wood PB, Patterson JC 2nd, Sunderland JJ et al. (2007) Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study. J Pain 8: 51–58
Yoldaş T, Ozgocmen S, Yildizhan H et al. (2003) Auditory p300 event-related potentials in fibromyalgia patients. Yonsei Med J 44: 89–93
Yücetürk TE, Yücel AE, Yücetürk H et al. (2005) Fibromyalgia: its prevalence in haemodialysis patients and its relationships with clinical and laboratory parameters. Nephrol Dial Transplant 20: 2485–2488
Yunus MB, Dailey JW, Aldag JC et al. (1992) Plasma and urinary catecholamines in primary fibromyalgia: a controlled study. J Rheumatol 19: 95–97
Yunus MB, Dailey JW, Aldag JC et al. (1992) Plasma tryptophan and other amino acids in primary fibromyalgia: a controlled study. J Rheumatol 19: 90–94
Yunus MB, Kalyan-Raman UP (1989) Muscle biopsy findings in primary fibromyalgia and other forms of nonarticular rheumatism. Rheum Dis Clin North Am 15: 115–134
Yunus MB, Khan MA, Rawlings KK et al. (1999) Genetic linkage analysis of multicase families with fibromyalgia syndrome. J Rheumatol 26: 408–412
Yunus MB, Young CS, Saeed SA et al. (2004) Positron emission tomography in patients with fibromyalgia syndrome and healthy controls. Arthritis Rheum 51: 513–518
Zidar J, Backman E, Bengtsson A et al. (1990) Quantitative EMG and muscle tension in painful muscles in fibromyalgia. Pain 40: 249–254
Zubieta JK, Heitzeg MM, Smith YR et al. (2003) COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Sci 299: 1240–1243
Interessenkonflikt
Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.
Author information
Authors and Affiliations
Corresponding author
Additional information
Die Mitgliedschaften der Autoren in Fachgesellschaften sind in Infobox 1 aufgelistet.
Rights and permissions
About this article
Cite this article
Sommer, C., Häuser, W., Gerhold, K. et al. Ätiopathogenese und Pathophysiologie des Fibromyalgiesyndroms und chronischer Schmerzen in mehreren Körperregionen. Schmerz 22, 267–282 (2008). https://doi.org/10.1007/s00482-008-0672-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00482-008-0672-6
Schlüsselwörter
- Fibromyalgiesyndrom (FMS)
- Schmerzen in mehreren Körperregionen
- Ätiopathogenese
- Pathophysiologie
- Systematischer Review