title: Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli.
abstract: Variations in the gene encoding catechol-O-methyltransferase (COMT) are linked to individual differences in pain sensitivity. A single nucleotide polymorphism (SNP) in codon 158 (val(158)met), which affects COMT protein stability, has been associated with the human experience of pain. We recently demonstrated that three common COMT haplotypes, which affect the efficiency of COMT translation, are strongly associated with a global measure of pain sensitivity derived from individuals' responses to noxious thermal, ischemic, and pressure stimuli. Specific haplotypes were associated with low (LPS), average (APS), or high (HPS) pain sensitivity. Although these haplotypes included the val(158)met SNP, a significant association with val(158)met variants was not observed. In the present study, we examined the association between COMT genotype and specific pain-evoking stimuli. Threshold and tolerance to thermal, ischemic, and mechanical stimuli, as well as temporal summation to heat pain, were determined. LPS/LPS homozygotes had the least, APS/APS homozygotes had average, and APS/HPS heterozygotes had the greatest pain responsiveness. Associations were strongest for measures of thermal pain. However, the rate of temporal summation of heat pain did not differ between haplotype combinations. In contrast, the val(158)met genotype was associated with the rate of temporal summation of heat pain, but not with the other pain measures. This suggests that the val(158)met SNP plays a primary role in variation in temporal summation of pain, but that other SNPs of the COMT haplotype exert a greater influence on resting nociceptive sensitivity. Here, we propose a mechanism whereby these two genetic polymorphisms differentially affect pain perception.
authors.affiliation: Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, NC, USA Australian Researcher Center for Population Oral Health, Dental School, University of Adelaide, Australia Department of Oral Medicine, Chulalongkorn University, Bangkok, Thailand NIDCR, NIH, DHHS, Bethesda, MD, USA NIAAA, NIH, DHHS, Rockville, MD, USA Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Nackley
authors.forename: Gary D
authors.initials: GD
authors.lastname: Slade
authors.forename: Kanokporn
authors.initials: K
authors.lastname: Bhalang
authors.forename: Inna
authors.initials: I
authors.lastname: Belfer
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Max
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: William
authors.initials: W
authors.lastname: Maixner
mesh_terms: D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D010146:Pain / Q000453:epidemiology* / Q000235:genetics*; D017288:Pain Threshold; D010812:Physical Stimulation / Q000379:methods*; D011110:Polymorphism, Genetic; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D002394:Catechol O-Methyltransferase