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ORIGINAL ARTICLEReumatismo, 2008; 60: Supplemento 1: 25-35Etiopathogenetic mechanisms of fibromyalgia syndromeMeccanismi eziopatogenetici della sindrome fibromialgicaS. Stisi 1 , M. Cazzola 2 , D. Buskila 3 , M. Spath 4 , M.A.Giamberardino 5 , P. Sarzi-Puttini 6 , G. Arioli 7 ,A. Alciati 8 , G. Leardini 9 , R. Gorla 10 , A. Marsico 11 , F. Ceccherelli 12 , L. Bazzichi 13 , R. Carignola 14 ,R.H. Gracely 15 , F. Salaffi 16 , F. Marinangeli 17 , R. Torta 18 , M. Di Franco 19 , G. Biasi 20 , G. Cassisi 21 ,R. Casale 22 , L. Altomonte 23 , F. Atzeni 6 (Italian Fibromyalgia Network)1Rheumatology Unit, “G.Rummo” Hospital, Benevento, Italy; 2 Unit of Rehabilitative Medicine “Hospital of Circolo”, Saronno (VA),Italy; 3 Department of Medicine H, Soroka Medical Center and Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel;4Friedrich-Baur-Institute, University of Munich, Germany; 5 Ce.S.I. “G. D’Annunzio” Foundation, Department of Medicine and Scienceof Aging, “G. D’Annunzio”, University of Chieti, Italy; 6 Rheumatology Unit, L. Sacco University Hospital, Milano, Italy; 7 Division ofRehabilitative Medicine and Rheumatology, General Hospital of Pieve di Coriano (Mantua), Italy; 8 Department of Psychiatry, L. SaccoUniversity Hospital, Milan, Italy; 9 Rheumatology Unit, SS Giovanni e Paolo Hospital , Venice, Italy; 10 Rheumatology and ClinicalImmunology, Spedali Civili and University of Brescia, Italy; 11 Rheumatology Unit, Hospital of Taranto, Taranto, Italy; 12 IOV (VenetoCancer Institute), IRCCS, Department of Pharmacology and Anesthesiology, University of Padua, Italy; 13 Department of InternalMedicine, Division of Rheumatology, S. Chiara Hospital, University of Pisa, Italy; 14 S.C.D.U. Internal Medicine I, Department ofClinical and Biological Science, University of Turin, Italy; 15 Department of Medicine, University of Michigan Medical School, AnnArbor, Michigan, USA; 16 Department of Rheumatology, Polytechnic University of the Marche Region, Ancona, Italy; 17 Department ofAnesthesiology and Pain Medicine, L'Aquila University, L'Aquila, Italy; 18 Department of Neuroscience, University of Torino,A.S.O. San Giovanni Battista of Turin, Turin, Italy; 19 Chair of Rheumatology, University la Sapienza Rome, Rome, Italy;20Unit of Rheumatology, University of Siena, Siena, Italy; 21 Rheumatology Branch, Specialist Outpatients’ Department, Belluno, Italy;22Department of Clinical Neurophysiology and Pain Rehabilitation Unit, Foundation Salvatore Maugeri, IRCCS, Scientific Instituteof Montescano, Montescano (PV), Italy; 23 UOC of Rheumatology Hospital S. Eugenio, Rome, ItalyCompeting interests: none declaredRIASSUNTOLa sindrome fibromialgica (FMS) è una comune condizione cronica di dolore diffuso con meccanismi causali largamentesconosciuti, ma la sua patogenesi appare associata ad una alterazione del sistema nocicettivo a livello del sistemanervoso centrale. La FMS è spesso scatenata da influenze ambientali negative, specialmente se presenti nell’infanzia.In un feto, questi triggers ambientali possono influenzare lo sviluppo del sistema nervosa autonomo (ASN) edell’asse ipotalamo-ipofisi-surrene (HPA). Frequente è la comorbidità di condizioni psicologiche che comprendonola depressione, gli attacchi di panico, l’ansia e il disturbo post-traumatico da stress (PTSD). Recenti evidenze suggerisconoche fattori genetici possano giocare un ruolo nella patogenesi della FMS. La sensibilizzazione centrale è statada tempo associata con il dolore fibromialgico. Questo fenomeno descrive l’aumentata eccitabilità dei neuroni dellecorna dorsali, che porta alla trasmissione di alterate informazioni nocicettive al cervello. La comprensione dellevie patogenetiche della FMS è supportata dall’osservazione delle risposte dei pazienti alle terapie neurofisiologicamentemirate e dalla ricerca di base.Reumatismo, 2008; 60: Supplemento 1: 25-35INTRODUCTIONFibromyalgia syndrome (FMS) is a commonchronic condition of widespread pain withcausal mechanisms that are largely unknown. It ischaracterized by moderate to severe musculoskel -Corresponding author:Piercarlo Sarzi-Puttini, MDDirector of Rheumatology UnitL. Sacco University Hospital, Milan, ItalyE-mail: sarzi@tiscali.itetal pain and allodynia, but its pathogenesis appearsconfined to the nociceptive structures of thecentral nervous system.From a pathogenetic point of view, indeed, no clearmuscle pathology has been demonstrated in FMS(1, 2), while increasing evidence suggests a disturbancein pain perception that is genetically conditioned.In our review we will consider five “keypoints”that we think determine the origin andmaintenance of the pain syndrome that we defineas fibromyalgia: “triggers,” “genetics,” “central
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