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Defective Endogenous Pain Modulation in Fibromyalgia: A Meta-Analysis of Temporal Summation and Conditioned Pain Modulation Paradigms

  • Anthony Terrence O'Brien
    Correspondence
    Address reprint requests to Anthony Terrence O'Brien, MD, Spaulding Rehabilitation Hospital, Harvard Medical School, Neuromodulation Center PM&R, 300 1st Avenue, Charlestown, MA, 02129.
    Affiliations
    Neuromodulation Center, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical, School, Boston, Massachusetts
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  • Alicia Deitos
    Affiliations
    Neuromodulation Center, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical, School, Boston, Massachusetts

    Laboratory of Pain & Neuromodulation, Hospital de Clínicas de Porto Alegre/Universidad de Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Post-graduate Program in Medical Sciences, School of Medicine, Universidad de Federal do Rio Grande do Sul, Porto Alegre, Brazil
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  • Yolanda Triñanes Pego
    Affiliations
    University of Santiago de Compostela, Santiago de Compostela, Department of Clinical Psychology and Psychobiology, A Coruña, Spain
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  • Felipe Fregni
    Affiliations
    Neuromodulation Center, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical, School, Boston, Massachusetts
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  • Maria Teresa Carrillo-de-la-Peña
    Affiliations
    Neuromodulation Center, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical, School, Boston, Massachusetts

    University of Santiago de Compostela, Santiago de Compostela, Department of Clinical Psychology and Psychobiology, A Coruña, Spain
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Published:February 15, 2018DOI:https://doi.org/10.1016/j.jpain.2018.01.010

      Highlights

      • We review temporal summation and conditioned pain modulation in fibromyalgia (FM).
      • Results revealed pain sensitization and defective endogenous pain modulation in FM.
      • Sensitivity analysis uncovered multiple modifying covariates.
      • Lack of blinding was a critical issue in most of the studies reviewed.
      • The paradigms studied may serve future diagnosis, treatment, and research on FM.

      Abstract

      To study the characteristics of temporal summation (TS) and conditioned pain modulation (CPM) in fibromyalgia (FM) patients, we systematically searched Pubmed and EMBASE for studies using TS or CPM comparing FM patients with healthy controls. We computed Hedges' g, risk of bias, sensitivity analysis, and meta-regression tests with 10,000 Monte-Carlo permutations. Twenty-three studies (625 female and 23 male FM patients and 591 female and 81 male healthy controls) were included. The meta-analyses showed an effect size of .53 for TS (P < .001; 95% confidence interval = .23–.83), which is a 68% relative difference between patients and controls, and of .57 for CPM (P < .001; 95% confidence interval = −.88 to −.26), representing a 65% relative difference between the groups. The qualitative analyses revealed large heterogeneity between study protocols. Although studies were of low risk of bias, lack of blinding was substantial. Sensitivity analysis and meta-regression identified type and site of stimulation, age, lab, sample size, and medication control as important sources of between-study variability. We showed a significant alteration of pain modulation mechanisms in FM patients.

      Perspective

      This novel meta-analysis provides evidence for defective endogenous pain modulation in FM patients. We explored the effect of covariates on between-study variability in these paradigms. These biomarkers may aid in diagnosis, and treatment of patients. However, validation requires further investigation under strict methodological settings, and into individual patient covariates.

      Key words

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