Review

. 2023 Jan;19(1):44-60.

doi: 10.1038/s41584-022-00873-6. Epub 2022 Dec 5.

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

Ana Margarida Pinto^{1

2

3}, Rinie Geenen^{4

5}, Tor D Wager⁶, Mark A Lumley⁷, Winfried Häuser⁸, Eva Kosek^{9

10}, Jacob N Ablin^{11

12}, Kirstine Amris¹³, Jaime Branco^{14

15}, Dan Buskila¹⁶, João Castelhano¹⁷, Miguel Castelo-Branco¹⁷, Leslie J Crofford¹⁸, Mary-Ann Fitzcharles¹⁹, Marina López-Solà²⁰, Mariana Luís²¹, Tiago Reis Marques^{22

23}, Philip J Mease^{24

25}, Filipe Palavra^{26

27}, Jamie L Rhudy²⁸, Lucina Q Uddin²⁹, Paula Castilho¹, Johannes W G Jacobs³⁰, José A P da Silva^{31

32

33}

Affiliations

¹ University of Coimbra, Center for Research in Neuropsychology and Cognitive and Behavioral Intervention (CINEICC), Faculty of Psychology and Educational Sciences, Coimbra, Portugal.
² University of Coimbra, University Clinic of Rheumatology, Faculty of Medicine, Coimbra, Portugal.
³ University of Coimbra, Psychological Medicine Institute, Faculty of Medicine, Coimbra, Portugal.
⁴ Department of Psychology, Utrecht University, Utrecht, The Netherlands.
⁵ Altrecht Psychosomatic Medicine Eikenboom, Zeist, The Netherlands.
⁶ Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.
⁷ Department of Psychology, Wayne State University, Detroit, MI, USA.
⁸ Department Psychosomatic Medicine and Psychotherapy, Technical University of Munich, Munich, Germany.
⁹ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
¹⁰ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
¹¹ Internal Medicine H, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
¹² Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
¹³ The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark.
¹⁴ Rheumatology Department, Egas Moniz Hospital - Lisboa Ocidental Hospital Centre (CHLO-EPE), Lisbon, Portugal.
¹⁵ Comprehensive Health Research Center (CHRC), Chronic Diseases Research Centre (CEDOC), NOVA Medical School, NOVA University Lisbon (NMS/UNL), Lisbon, Portugal.
¹⁶ Ben Gurion University of the Negev Beer-Sheba, Beersheba, Israel.
¹⁷ University of Coimbra, Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), ICNAS, Coimbra, Portugal.
¹⁸ Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁹ Division of Rheumatology, Department of Medicine, McGill University, Montreal, QC, Canada.
²⁰ Serra Hunter Programme, Department of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
²¹ Rheumatology Department, Coimbra Hospital and University Centre, Coimbra, Portugal.
²² Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Hammersmith Hospital, Imperial College London, London, UK.
²³ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁴ Swedish Medical Center/Providence St. Joseph Health, Seattle, WA, USA.
²⁵ University of Washington School of Medicine, Seattle, WA, USA.
²⁶ Centre for Child Development, Neuropediatric Unit, Paediatric Hospital, Coimbra Hospital and University Centre, Coimbra, Portugal.
²⁷ University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (i.CBR), Faculty of Medicine, Coimbra, Portugal.
²⁸ Department of Psychology, University of Tulsa, Tulsa, OK, USA.
²⁹ Department of Psychology, University of Miami, Coral Gables, FL, USA.
³⁰ Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
³¹ University of Coimbra, University Clinic of Rheumatology, Faculty of Medicine, Coimbra, Portugal. jdasilva@chuc.min-saude.pt.
³² Rheumatology Department, Coimbra Hospital and University Centre, Coimbra, Portugal. jdasilva@chuc.min-saude.pt.
³³ University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (i.CBR), Faculty of Medicine, Coimbra, Portugal. jdasilva@chuc.min-saude.pt.

PMID: 36471023
DOI: 10.1038/s41584-022-00873-6

Review

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

Ana Margarida Pinto et al. Nat Rev Rheumatol. 2023 Jan.

. 2023 Jan;19(1):44-60.

doi: 10.1038/s41584-022-00873-6. Epub 2022 Dec 5.

Authors

Affiliations

¹ University of Coimbra, Center for Research in Neuropsychology and Cognitive and Behavioral Intervention (CINEICC), Faculty of Psychology and Educational Sciences, Coimbra, Portugal.
² University of Coimbra, University Clinic of Rheumatology, Faculty of Medicine, Coimbra, Portugal.
³ University of Coimbra, Psychological Medicine Institute, Faculty of Medicine, Coimbra, Portugal.
⁴ Department of Psychology, Utrecht University, Utrecht, The Netherlands.
⁵ Altrecht Psychosomatic Medicine Eikenboom, Zeist, The Netherlands.
⁶ Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.
⁷ Department of Psychology, Wayne State University, Detroit, MI, USA.
⁸ Department Psychosomatic Medicine and Psychotherapy, Technical University of Munich, Munich, Germany.
⁹ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
¹⁰ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
¹¹ Internal Medicine H, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
¹² Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
¹³ The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark.
¹⁴ Rheumatology Department, Egas Moniz Hospital - Lisboa Ocidental Hospital Centre (CHLO-EPE), Lisbon, Portugal.
¹⁵ Comprehensive Health Research Center (CHRC), Chronic Diseases Research Centre (CEDOC), NOVA Medical School, NOVA University Lisbon (NMS/UNL), Lisbon, Portugal.
¹⁶ Ben Gurion University of the Negev Beer-Sheba, Beersheba, Israel.
¹⁷ University of Coimbra, Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), ICNAS, Coimbra, Portugal.
¹⁸ Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁹ Division of Rheumatology, Department of Medicine, McGill University, Montreal, QC, Canada.
²⁰ Serra Hunter Programme, Department of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
²¹ Rheumatology Department, Coimbra Hospital and University Centre, Coimbra, Portugal.
²² Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Hammersmith Hospital, Imperial College London, London, UK.
²³ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁴ Swedish Medical Center/Providence St. Joseph Health, Seattle, WA, USA.
²⁵ University of Washington School of Medicine, Seattle, WA, USA.
²⁶ Centre for Child Development, Neuropediatric Unit, Paediatric Hospital, Coimbra Hospital and University Centre, Coimbra, Portugal.
²⁷ University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (i.CBR), Faculty of Medicine, Coimbra, Portugal.
²⁸ Department of Psychology, University of Tulsa, Tulsa, OK, USA.
²⁹ Department of Psychology, University of Miami, Coral Gables, FL, USA.
³⁰ Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
³¹ University of Coimbra, University Clinic of Rheumatology, Faculty of Medicine, Coimbra, Portugal. jdasilva@chuc.min-saude.pt.
³² Rheumatology Department, Coimbra Hospital and University Centre, Coimbra, Portugal. jdasilva@chuc.min-saude.pt.
³³ University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (i.CBR), Faculty of Medicine, Coimbra, Portugal. jdasilva@chuc.min-saude.pt.

PMID: 36471023
DOI: 10.1038/s41584-022-00873-6

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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Comment in

Imbalance of threat and soothing systems in fibromyalgia: rephrasing an established mechanistic model?
Martínez-Lavín M. Martínez-Lavín M. Nat Rev Rheumatol. 2023 May;19(5):318. doi: 10.1038/s41584-023-00949-x. Nat Rev Rheumatol. 2023. PMID: 36959281 No abstract available.
Reply to 'Imbalance of threat and soothing systems in fibromyalgia: rephrasing an established mechanistic model?'.
Pinto AM, Geenen R, Wager TD, Lumley MA, Häuser W, Kosek E, Ablin JN, Amris K, Branco J, Buskila D, Castelhano J, Castelo-Branco M, Crofford LJ, Fitzcharles MA, López-Solà M, Luís M, Marques TR, Mease PJ, Palavra F, Rhudy JL, Uddin LQ, Castilho P, Jacobs JWG, da Silva JAP. Pinto AM, et al. Nat Rev Rheumatol. 2023 May;19(5):319-320. doi: 10.1038/s41584-023-00950-4. Nat Rev Rheumatol. 2023. PMID: 36959282 No abstract available.
Hypothetical model ignores many important pathophysiologic mechanisms in fibromyalgia.
Clauw DJ, Choy EHS, Napadow V, Soni A, Boehnke KF, Naliboff B, Hassett AL, Arewasikporn A, Schrepf A, Kaplan CM, Williams D, Basu N, Bergmans RS, Harris RE, Harte SE, Chadwick A, Macfarlane GJ. Clauw DJ, et al. Nat Rev Rheumatol. 2023 May;19(5):321. doi: 10.1038/s41584-023-00951-3. Nat Rev Rheumatol. 2023. PMID: 36964334 Free PMC article. No abstract available.
Reply to: Hypothetical model ignores many important pathophysiologic mechanisms in fibromyalgia.
Pinto AM, Geenen R, Wager TD, Häuser W, Kosek E, Ablin JN, Amris K, Branco J, Buskila D, Castelhano J, Castelo-Branco M, Crofford LJ, Fitzcharles MA, López-Solà M, Luís M, Marques TR, Mease PJ, Palavra F, Rhudy JL, Uddin LQ, Castilho P, Jacobs JWG, da Silva JAP. Pinto AM, et al. Nat Rev Rheumatol. 2023 May;19(5):322-323. doi: 10.1038/s41584-023-00952-2. Nat Rev Rheumatol. 2023. PMID: 36964336 No abstract available.

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

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

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