COMT haplotypes contributing to pain sensitivity and painful TMD

Objectives: We examined the association of 6 highly abundant SNPs in the catecholamine-O-methyl-transferase (COMT) gene with individual variations in pain sensitivity and related it to the likelihood of developing a painful temporomandibular disorder (TMD). Methods: We genotyped 240 healthy females who participated in a 3-year prospective cohort study. Subjects were phenotyped with respect to their sensitivity to noxious thermal, mechanical, and ischemic stimuli. These measurements were combined to produce an aggregate (i.e., summed) pain z-score for each participant. Summed z-scores were correlated with the 6 COMT SNPs. Results: Four SNP’s rs6269, rs4633, rs4818 and rs4680 showed significant correlation with individual summed z-scores. These SNPs formed three major haplotypes. Each haplotype was associated with different mean z-scores, and consequently reflected different levels of pain sensitivity. Individuals homozygous for the most frequent haplotype were relatively sensitive to pain-evoking stimuli (mean z-score = -1.09, sem=±1.5). Individuals homozygous for the second most frequent haplotype were the least sensitive to pain-evoking stimuli (mean z-score = 5.27, sem = ± 1.4). Individuals who possessed the least frequent haplotype with one of the two more common haplotypes were significantly more sensitive to pain-evoking stimuli than the corresponding individuals who were homozygous for either of the two major haplotypes Fifteen initially pain-free female subjects were diagnosed with recent onset TMD during the three-year observational period. When evaluated statistically, we found that individuals who beared at least one haplotype associated with less pain sensitivity had the rate of TMD onset 2.6 times lower (P<0.05, 95%CI=1.3 – 5.3) then the remaining subjects. Conclusions: Polymorphism (haplotypes) in the COMT gene plays a significant role in individual variations in pain sensitivity and it is one of several likely genetic factors that contributes to the development of TMD in women. Supported by DE07509, DE007333, DE00366, AA000301, and USUHS G192BR-C4 grants.