In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the brain response to heat pain stimuli in 54 subjects genotyped for the common COMT val158met polymorphism (val/val = n 22, val/met = n 20, met/met = n 12).
More generally, apart from one report that focused on pain-induced opioid release, this is the first functional neuroimaging study showing an effect of the COMT val158met polymorphism on cerebral pain processing.
Genetics-based personalized approaches to pain management have received a setback because of the nonreproducibility of functional genetic associations such as the pain-modulatory effect of the catechol-O-methyl transferase (COMT) gene 472G>A single-nucleotide polymorphism.
Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous (val(158)met) position, designated as low (LPS), average (APS), and high pain sensitive (HPS), are associated with experimental pain sensitivity and risk of developing chronic musculoskeletal pain conditions.
It is shown that a polymorphism in the COMT gene, Rs4680 (Val158Met), influence pain sensitivity in human experimental pain and the efficacy for morphine in cancer pain treatment.
This suggests that the val(1</span>58)met SNP plays a primary role in variation in temporal summation of pai</span>n, but that other SNPs of the COMT haplotype exert a greater influence on resting nociceptive sensitivity.
The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, that has been found to influence human pain perception, and one study has found that migraine was less likely among those with the Val/Val polymorphism.
A single nucleotide polymorphism (Val158Met) of COMT leads to a three to four fold reduction in the activity of the enzyme and has been associated to modifications in the response to a pain stressor.
The COMT val158met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli.