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

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.PerspectiveThe 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.