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Reply to ‘Imbalance of threat and soothing systems in fibromyalgia: rephrasing an established mechanistic model?’

Nature Reviews Rheumatology volume 19, pages 319–320 (2023)Cite this article

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We read with interest the correspondence by Manuel Martínez-Lavín on our Perspective article (Pinto, A. M. et al. Emotion regulation and the salience network: a hypothetical integrative model of fibromyalgia. Nat. Rev. Rheumatol. 19, 44–60 (2023))1, which argues that our proposed ‘Fibromyalgia: Imbalance of Threat and Soothing Systems (FITTS)’ model echoes the existing view of fibromyalgia as a stress-evoked sympathetically maintained neuropathic pain syndrome (Martínez-Lavín, M. Imbalance of threat and soothing systems in fibromyalgia: rephrasing an established mechanistic model? Nat. Rev. Rheumatol. https://doi.org/10.1038/s41584-023-00949-x (2023))2. Specifically, Martínez-Lavín2 proposes that various stressors (for example, physical, psychosocial, infectious and autoimmune) lead to dorsal root ganglion neuroplasticity, which is ‘the’ primary driver of pain3.

In our view, a core challenge in the pathophysiology of fibromyalgia is the reconciliation of the many potential mechanisms involved, their relative importance and their roles as causes or consequences of fibromyalgia. We dedicated our paper to this aim, but this probably cannot be fully accomplished. The pathophysiology of fibromyalgia is too complex for a unidimensional view, which Martínez-Lavín seems to recognize when stating elsewhere4 that fibromyalgia “cannot be explained by the prevailing linear-reductionist medical paradigm”. There may be several potential origins, but once the vicious circle is established, it is almost impossible — and probably irrelevant — to separate the egg from the chicken.

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References

  1. Pinto, A. M. et al. Emotion regulation and the salience network: a hypothetical integrative model of fibromyalgia. Nat. Rev. Rheumatol. 19, 44–60 (2023).

    Article  PubMed  Google Scholar 

  2. Martínez-Lavín, M. Imbalance of threat and soothing systems in fibromyalgia: rephrasing an established mechanistic model? Nat. Rev. Rheumatol. https://doi.org/10.1038/s41584-023-00949-x (2023).

    Article  PubMed  Google Scholar 

  3. Martínez-Lavín, M. Dorsal root ganglia: fibromyalgia pain factory? Clin. Rheumatol. 40, 783–787 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Martínez-Lavín, M., Infante, O. & Lerma, C. Hypothesis: the chaos and complexity theory may help our understanding of fibromyalgia and similar maladies. Semin. Arthritis Rheum. 37, 260–264 (2008).

    Article  PubMed  Google Scholar 

  5. Harte, S. E. et al. Reduced intraepidermal nerve fiber density after a sustained increase in insular glutamate: a proof-of-concept study examining the pathogenesis of small fiber pathology in fibromyalgia. Pain Rep. 2, e590 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Grayston, R. et al. A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: implications for a new paradigm in fibromyalgia etiopathogenesis. Semin. Arthritis Rheum. 48, 933–940 (2018).

    Article  PubMed  Google Scholar 

  7. Sommer, C. & Üçeyler, N. Small fiber pathology in pain syndromes. in Small Fiber Neuropathy and Related Syndromes: Pain and Neurodegeneration (eds. Hsieh, S.-T. et al.) 121–129 (Springer Singapore, 2019).

  8. Martínez-Lavín, M. Fibromyalgia and small fiber neuropathy: the plot thickens! Clin. Rheumatol. 37, 3167–3171 (2018).

    Article  PubMed  Google Scholar 

  9. Brosschot, J. F., Verkuil, B. & Thayer, J. F. Generalized unsafety theory of stress: unsafe environments and conditions, and the default stress response. Int. J. Environ. Res. Public Health 15, 464 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kolacz, J. & Porges, S. W. Chronic Diffuse pain and functional gastrointestinal disorders after traumatic stress: pathophysiology through a polyvagal perspective. Front. Med. 5, 145 (2018).

    Article  Google Scholar 

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Author information

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 of 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, Quebec, Canada

    Mary-Ann Fitzcharles

  20. Serra Hunter Programme, Department of Medicine and Health Sciences, Institute of Neuroscience, 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, The Netherlands

    Johannes W. G. Jacobs

Authors
  1. Ana Margarida Pinto
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  2. Rinie Geenen
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  3. Tor D. Wager
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  4. Mark A. Lumley
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  5. Winfried Häuser
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  6. Eva Kosek
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  7. Jacob N. Ablin
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  8. Kirstine Amris
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  9. Jaime Branco
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  10. Dan Buskila
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  11. João Castelhano
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  12. Miguel Castelo-Branco
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  13. Leslie J. Crofford
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  14. Mary-Ann Fitzcharles
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  15. Marina López-Solà
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  16. Mariana Luís
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  17. Tiago Reis Marques
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  18. Philip J. Mease
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  19. Filipe Palavra
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  20. Jamie L. Rhudy
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  21. Lucina Q. Uddin
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  22. Paula Castilho
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  23. Johannes W. G. Jacobs
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  24. José A. P. da Silva
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Corresponding author

Correspondence to José A. P. da Silva.

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The authors declare no competing interests.

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Cite this article

Pinto, A.M., Geenen, R., Wager, T.D. et al. Reply to ‘Imbalance of threat and soothing systems in fibromyalgia: rephrasing an established mechanistic model?’. Nat Rev Rheumatol 19, 319–320 (2023). https://doi.org/10.1038/s41584-023-00950-4

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  • DOI: https://doi.org/10.1038/s41584-023-00950-4

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