Genetic variation in catechol‐O‐methyltransferase is associated with individual differences in conditioned pain modulation in healthy subjects. (3rd July 2021)

• Record Type: Journal Article
• Authors: Korczeniewska, Olga A.; Kuo, Fengshen; Huang, Ching‐Yu; Nasri‐Heir, Cibele; Khan, Junad; Benoliel, Rafael; Hirschberg, Craig; Eliav, Eli; Diehl, Scott R.
• Is Part Of: Journal of gene medicine. Volume 23:Number 11(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-03
• Subjects: catechol‐O‐methyltransferase -- conditioned pain modulation -- haplotype -- single nucleotide polymorphism; Genetic transformation -- Periodicals; Gene Transfer -- Periodicals; Gene Therapy -- Periodicals; 616.042
• DOI: 10.1002/jgm.3374
• Languages: English
• ISSNs: 1099-498X

Abstract

Abstract: Background: Genetic variation in the catechol‐ O ‐methyltransferase ( COMT ) gene is associated with sensitivity to both acute experimental pain and chronic pain conditions. Four single nucleotide polymorphisms (SNPs) have traditionally been used to infer three common haplotypes designated as low, average and high pain sensitivity and are reported to affect both COMT enzymatic activity and pain sensitivity. One mechanism that may partly explain individual differences in sensitivity to pain is conditioned pain modulation (CPM). We hypothesized that variation in CPM may have a genetic basis. Methods: We evaluated CPM in 77 healthy pain‐free Caucasian subjects by applying repeated mechanical stimuli to the dominant forearm using 26‐g von Frey filament as the test stimulus with immersion of the non‐dominant hand in hot water as the conditioning stimulus. We assayed COMT SNP genotypes by the TaqMan method using DNA extracted from saliva. Results: SNP rs4680 ( val 158 met ) was not associated with individual differences in CPM. However, CPM was associated with COMT low pain sensitivity haplotypes under an additive model ( p = 0.004) and the effect was independent of gender. Conclusions: We show that, although four SNPs are used to infer COMT haplotypes, the low pain sensitivity haplotype is determined by SNP rs6269 (located in the 5′ regulatory region of COMT ), suggesting that inherited variation in gene expression may underlie individual differences in pain modulation. Analysis of 13 global populations revealed that the COMT low pain sensitivity haplotype varies in frequency from 13% to 44% and showed that two SNPs are sufficient to distinguish all COMT haplotypes in most populations. Abstract : Conditioned pain modulation is associated with the number of COMT gene low pain sensitivity (LPS) haplotypes. Healthy individuals with two LPS haplotypes have significantly more efficient conditioned pain modulation compared to those with zero or one LPS.