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This invited review updates understanding of FM pathophysiology and management, emphasizing recent progress in both pharmacologic and non-pharmacologic strategies. Multifactorial mechanisms involve central and peripheral nervous systems, psychosocial stressors, the HPA axis, autonomic activity, and immune contributions, with obesity and obstructive sleep apnea as additional factors. Diagnosis relies on a systematic clinical approach, with education, psychotherapy, exercise, and sleep optimization as first-line care, and pharmacotherapy added for symptom control. 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D. Hiser3, Deanna L. K. Hill4, Julia O. Farmer5  \nORCID iDs of the authors:  \nE.W. 0009-0005-4354-722X;  \nA. B. 0009-0002-0285-8804;  \nJ. K. D. H. 0009-0008-1829-8876;  \nD. L. K. H. 0009-0009-6243-9637;  \nJ.O. F. 0009-0004-3704-4813.  \nCite this article as: Wu E, Brener A, Hiser JKD, Hill DLK, Farmer JO. Fibromyalgia: Update on pathogenesis and management. Eur J Rheumatol. 2025, 12(4), 0032, doi:10 . 5152/ eurjrheum.2025.25032.  \n1 University of California, San Diego, Revelle College, California, United States  \n2 University of California, San Diego School of Medicine, California, United States  \n3 University of California, San Diego Internal Medicine, California, United States  \n4 University of California, San Diego Internal Medicine, General Internal Medicine, California, United States  \n5 Rheumatology and Arthritis Medical Clinic, California, United States  \n*These authors contributed equally to this work and share first authorship.  \nCorresponding author: Julia O. Farmer [E-mail: julrhi@gmail.com](E-mail: julrhi@gmail.com)  \n[Received: April 1](Received: April 1), 2025  \nRevision Requested: May 20, 2025  \nLast Revision Received: June 28, 2025  \nAccepted: July 8, 2025  \nPublication Date: December 5, 2025  \nCopyright@Author(s) -Available online at [www.eurjrheumatol.org](www.eurjrheumatol.org).  \nContent of this journal is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.  \nAbstract  \nFibromyalgia (FM) is a complex disorder characterized by chronic widespread pain, fatigue, sleep disturbances, mood alterations, and cognitive impairment. This review aims to provide an updated understanding of pathophysiology and management, highlighting recent advances in both pharmacologic and non-pharmacologic treatment options. Multifactorial pathophysiology includes the central and peripheral nervous systems, psychosocial stressors, the hypothalamic–pituitary–adrenal axis, the autonomic nervous system, and the immune system. Obesity and obstructive sleep apnea are also significant contributors. Diagnosis is clinical and requires a systematic approach. Nonpharmacologic treatments, including education, psychotherapy, exercise, and sleep optimization, are first-line management. Pharmacotherapy is offered to patients who need additional symptom control, and evidence for the most promising options is discussed. The review underscores the importance of a multidisciplinary approach to improve quality of life and suggests potential future directions for FM management.  \nKeywords: Fibromyalgia, nociplastic, pain, serotonin, pregabalin, naltrexone  \nIntroduction  \nFibromyalgia (FM) is a nociplastic disease of protean manifestations which has frustrated patients and challenged rheumatology, neurology, primary care, and rehabilitation communities for decades. Recently, significant advances have been made in our understanding of the multifactorial and eminently complex pathophysiology of this debilitating widespread pain disorder. Similar progress has been made in treatment options, both pharmacologic and non-pharmacologic. The aim of the present review is to introduce pathophysiology, clinical manifestations, and diagnosis, as well as current evidence-based treatment options, both pharmacologic and non-pharmacologic. The authors also hope to provide insight into and stimulate discussion of potential future directions for therapy based on new treatment options heretofore underutilized or not even considered in FM management. The authors hope to appeal to primary care as well as specialty audiences, with a discussion of current options and future directions for multidisciplinary care.  \nEpidemiology  \nFibromyalgia is the third most common musculoskeletal disorder following low back pain and osteoarthritis. The estimated worldwide prev","cbCaint9pPBdRbzx","https://ap.wps.com/l/cbCaint9pPBdRbzx","pdf",436846,"English","# Abstract\n# Introduction\n# Epidemiology\n# Clinical Manifestations","[{\"question\":\"What symptoms characterize fibromyalgia?\",\"answer\":\"Fibromyalgia is characterized by chronic widespread pain along with fatigue, sleep disturbances, mood alterations, and cognitive impairment.\"},{\"question\":\"What factors are involved in fibromyalgia pathophysiology?\",\"answer\":\"The review highlights multifactorial mechanisms including central and peripheral nervous system involvement, psychosocial stressors, the hypothalamic–pituitary–adrenal axis, the autonomic nervous system, the immune system, plus obesity and obstructive sleep apnea.\"},{\"question\":\"How is fibromyalgia diagnosed and managed?\",\"answer\":\"Diagnosis is clinical and requires a systematic approach. First-line management emphasizes nonpharmacologic care such as education, psychotherapy, exercise, and sleep optimization, while pharmacotherapy is used when additional symptom control is needed.\"}]","Fibromyalgia: Update on Pathogenesis and Management | PDF",1790691724]