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Central Pain Sensitization, COMT Val158Met Polymorphism, and Emotional Factors in Fibromyalgia

  • Jules Desmeules
    Correspondence
    Address reprint requests to Jules Desmeules, MD, Geneva University Hospitals, Division of Clinical Pharmacology & Toxicology, Multidisciplinary Pain Center, Gabrielle Perret-Gentil 4, 1211 Geneva 14, Switzerland.
    Affiliations
    Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland

    Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland
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  • Jocelyne Chabert
    Affiliations
    Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland
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  • Michela Rebsamen
    Affiliations
    Division of Laboratory Medicine, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland
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  • Elisabetta Rapiti
    Affiliations
    Institute for Social and Preventive Medicine, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland
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  • Valerie Piguet
    Affiliations
    Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland

    Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland
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  • Marie Besson
    Affiliations
    Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland

    Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland
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  • Pierre Dayer
    Affiliations
    Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland

    Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland
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  • Christine Cedraschi
    Affiliations
    Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland

    Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland

    Division of General Medical Rehabilitation, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland
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Published:December 16, 2013DOI:https://doi.org/10.1016/j.jpain.2013.10.004

      Abstract

      Neurobiological evidence points to altered central nervous system processing of nociceptive stimuli in fibromyalgia. Enzymes like catechol-O-methyl-transferase (COMT) are involved in the elimination of catecholamines playing a possible role in central sensitization and pain. We used quantitative sensory testing to evidence central sensitization in fibromyalgia patients and test whether COMTVal158Met polymorphism, associated with a reduction in enzyme activity, plays a role in sensitized patients. Pain evaluation and quantitative sensory testing were performed including the spinal nociceptive flexion reflex, a physiologic correlate for the evaluation of central nociceptive pathways. Quality of life and distress questionnaires were used. A total of 137 fibromyalgia patients were assessed and compared to 99 matched controls. Central sensitization (nociceptive flexion reflex <27 mA) was present in 95/134 (71%) patients. Among them, COMT p.Val158Met polymorphism displayed a significant linear “genotype effect” (P = .033), with the Met/Met (mean = 17.8 ± 4.8 mA) and Val/Val (mean = 21.4 ± 4.6 mA) subgroups at the opposite ends of the nociceptive flexion reflex threshold (Met/Met vs Val/Val P = .015) and the Val/Met subgroup (mean = 19 ± 4.9 mA) in between (Val/Met vs Val/Val P = .041). Spontaneous moderate to severe pain was more likely to be associated with COMT Met/Met genotype. Patients showed important emotional distress compared to controls. In sensitized patients, the COMT Met/Met subgroup showed systematically—though not significantly—worse scores for all psychological variables.

      Perspective

      The association between COMT p.Val158Met polymorphism and central sensitization in fibromyalgia is essential as it refers to the severity of central sensitization and may be a risk factor for treatment outcome.

      Key words

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