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

Nature Reviews Rheumatology volume 19, pages 44–60 (2023)Cite this article

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Abstract

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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Fig. 1: Potential pathophysiological processes in fibromyalgia.
Fig. 2: Central sensitivity syndromes and chronic overlapping pain conditions.
Fig. 3: The threat–safeness (im)balance model of fibromyalgia.
Fig. 4: An integrative model of fibromyalgia.
Fig. 5: Development of threat–safeness (im)balance and opportunities for intervention.

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Acknowledgements

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.

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Authors and Affiliations

  1. University of Coimbra, Center for Research in Neuropsychology and Cognitive and Behavioral Intervention (CINEICC), Faculty of Psychology and Educational Sciences, Coimbra, Portugal

    Ana Margarida Pinto & Paula Castilho

  2. University of Coimbra, University Clinic of Rheumatology, Faculty of Medicine, Coimbra, Portugal

    Ana Margarida Pinto & José A. P. da Silva

  3. University of Coimbra, Psychological Medicine Institute, Faculty of Medicine, Coimbra, Portugal

    Ana Margarida Pinto

  4. Department of Psychology, Utrecht University, Utrecht, The Netherlands

    Rinie Geenen

  5. Altrecht Psychosomatic Medicine Eikenboom, Zeist, The Netherlands

    Rinie Geenen

  6. Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA

    Tor D. Wager

  7. Department of Psychology, Wayne State University, Detroit, MI, USA

    Mark A. Lumley

  8. Department Psychosomatic Medicine and Psychotherapy, Technical University of Munich, Munich, Germany

    Winfried Häuser

  9. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden

    Eva Kosek

  10. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

    Eva Kosek

  11. Internal Medicine H, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel

    Jacob N. Ablin

  12. Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel

    Jacob N. Ablin

  13. The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark

    Kirstine Amris

  14. Rheumatology Department, Egas Moniz Hospital — Lisboa Ocidental Hospital Centre (CHLO-EPE), Lisbon, Portugal

    Jaime Branco

  15. Comprehensive Health Research Center (CHRC), Chronic Diseases Research Centre (CEDOC), NOVA Medical School, NOVA University Lisbon (NMS/UNL), Lisbon, Portugal

    Jaime Branco

  16. Ben Gurion University of the Negev Beer-Sheba, Beersheba, Israel

    Dan Buskila

  17. University of Coimbra, Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), ICNAS, Coimbra, Portugal

    João Castelhano & Miguel Castelo-Branco

  18. Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Leslie J. Crofford

  19. Division of Rheumatology, Department of Medicine, McGill University, Montreal, QC, Canada

    Mary-Ann Fitzcharles

  20. Serra Hunter Programme, Department of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain

    Marina López-Solà

  21. Rheumatology Department, Coimbra Hospital and University Centre, Coimbra, Portugal

    Mariana Luís & José A. P. da Silva

  22. Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Hammersmith Hospital, Imperial College London, London, UK

    Tiago Reis Marques

  23. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Tiago Reis Marques

  24. Swedish Medical Center/Providence St. Joseph Health, Seattle, WA, USA

    Philip J. Mease

  25. University of Washington School of Medicine, Seattle, WA, USA

    Philip J. Mease

  26. Centre for Child Development, Neuropediatric Unit, Paediatric Hospital, Coimbra Hospital and University Centre, Coimbra, Portugal

    Filipe Palavra

  27. University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (i.CBR), Faculty of Medicine, Coimbra, Portugal

    Filipe Palavra & José A. P. da Silva

  28. Department of Psychology, University of Tulsa, Tulsa, OK, USA

    Jamie L. Rhudy

  29. Department of Psychology, University of Miami, Coral Gables, FL, USA

    Lucina Q. Uddin

  30. Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands

    Johannes W. G. Jacobs

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Contributions

A.M.P., F.P., M.L. and R.G. researched data for the article. J.A.P.S., A.M.P., R.G., E.K. and M.L. wrote the article. J.A.P.S., A.M.P., R.G., T.D.W., M.A.L., W.H., E.K., M.L.-S., J.L.R. and J.W.G.J. made a substantial contribution to discussion of the content. All authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to José A. P. da Silva.

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Competing interests

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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Nature Reviews Rheumatology thanks S. Duschek, G. Littlejohn and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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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

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