Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive ‘threat’ system and underactive ‘soothing’ system, might keep the ‘salience network’ (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.
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A.M.P. is the holder of a PhD Grant (SFRH/BD/145954/2019), sponsored by the Portuguese Foundation for Science and Technology (FCT), the Human Capital Operational Programme (POCH) and the European Union (EU), and was financially supported (through a stipend) for this work by the Coimbra Rheumatology Association (ARCo) and the Portuguese Society of Rheumatology (SPR). M.L.-S. is a Serra Hunter Lecturer Professor at the School of Medicine, University of Barcelona.
E.K. reports personal fees from Eli Lilly, Sandoz and UCB Pharma, outside the submitted work. T.R.M. reports personal fees from Lundbeck, Astellas, Janssen and Angelini outside the submitted work. R.G., T.D.W., M.A.L., W.H., J.N.A., K.A., J.B., D.B., J.C., M.C.-B., L.J.C., M.-A.F., M.L.-S., M.L., P.J.M., F.P., J.L.R., L.Q.U., P.C., J.W.G.J. and J.A.P.S. declare no competing interests.
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Pinto, A.M., Geenen, R., Wager, T.D. et al. Emotion regulation and the salience network: a hypothetical integrative model of fibromyalgia. Nat Rev Rheumatol 19, 44–60 (2023). https://doi.org/10.1038/s41584-022-00873-6