title: Modification of COMT-dependent pain sensitivity by psychological stress and sex.
abstract: Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study, including 2 cohorts, one of 2972 subjects tested for thermal pain sensitivity (Orofacial Pain: Prospective Evaluation and Risk Assessment) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-motor vehicle collision). In both cohorts, the COMT high-pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in nonstressed individuals, but not in stressed individuals. In the post-motor vehicle collision cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity.
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, McGill University Genome Building, Montreal, QC, Canada Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Center for Pain Research and Innovation, University of North Carolina at Chapel Hill; Department of Endodontics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Center for Translational Pain Medicine, Duke University, Durham, NC, USA Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA; Brotman Facial Pain Center, University of Maryland School of Dentistry, Baltimore, MD, USA Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Community Dentistry and Behavioral Science, University of Florida, College of Dentistry, and Pain, Research and Intervention Center of Excellence, Gainesville, FL, USA Department of Oral Diagnostic Sciences, University at Buffalo, Buffalo, NY, USA.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Meloto
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Bortsov
authors.forename: Eric
authors.initials: E
authors.lastname: Bair
authors.forename: Erika
authors.initials: E
authors.lastname: Helgeson
authors.forename: Cara
authors.initials: C
authors.lastname: Ostrom
authors.forename: Shad B
authors.initials: SB
authors.lastname: Smith
authors.forename: Ronald
authors.initials: R
authors.lastname: Dubner
authors.forename: Gary D
authors.initials: GD
authors.lastname: Slade
authors.forename: Roger B
authors.initials: RB
authors.lastname: Fillingim
authors.forename: Joel D
authors.initials: JD
authors.lastname: Greenspan
authors.forename: Richard
authors.initials: R
authors.lastname: Ohrbach
authors.forename: William
authors.initials: W
authors.lastname: Maixner
authors.forename: Samuel A
authors.initials: SA
authors.lastname: McLean
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000502:physiology*; D006801:Humans; D008297:Male; D010146:Pain / Q000150:complications / Q000235:genetics / Q000523:psychology*; D017288:Pain Threshold / Q000502:physiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D013315:Stress, Psychological / Q000523:psychology*
chemical_list: D002394:Catechol O-Methyltransferase