Emotion regulation and the salience network: a hypothetical integrative model of fibromyalgia

Ana Margarida Pinto, Rinie Geenen, Tor D. Wager, Mark A. Lumley, Winfried Häuser, Eva Kosek, Jacob N. Ablin, Kirstine Amris, Jaime Branco, Dan Buskila, João Castelhano, Miguel Castelo-Branco, Leslie J. Crofford, Mary Ann Fitzcharles, Marina López-Solà, Mariana Luís, Tiago Reis Marques, Philip J. Mease, Filipe Palavra, Jamie L. RhudyLucina Q. Uddin, Paula Castilho, Johannes W.G. Jacobs, José A.P. da Silva

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)44-60
JournalNature Reviews Rheumatology
Issue number1
Early online date2022
Publication statusPublished - Jan 2023


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