Genetic basis for individual variations in pain perception and the development of a chronic pain condition.

Published

Journal Article

Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened pain sensitivity. We identified three genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase (COMT) that we designated as low pain sensitivity (LPS), average pain sensitivity (APS) and high pain sensitivity (HPS). We show that these haplotypes encompass 96% of the human population, and five combinations of these haplotypes are strongly associated (P=0.0004) with variation in the sensitivity to experimental pain. The presence of even a single LPS haplotype diminishes, by as much as 2.3 times, the risk of developing myogenous temporomandibular joint disorder (TMD), a common musculoskeletal pain condition. The LPS haplotype produces much higher levels of COMT enzymatic activity when compared with the APS or HPS haplotypes. Inhibition of COMT in the rat results in a profound increase in pain sensitivity. Thus, COMT activity substantially influences pain sensitivity, and the three major haplotypes determine COMT activity in humans that inversely correlates with pain sensitivity and the risk of developing TMD.

Full Text

Duke Authors

Cited Authors

  • Diatchenko, L; Slade, GD; Nackley, AG; Bhalang, K; Sigurdsson, A; Belfer, I; Goldman, D; Xu, K; Shabalina, SA; Shagin, D; Max, MB; Makarov, SS; Maixner, W

Published Date

  • January 2005

Published In

Volume / Issue

  • 14 / 1

Start / End Page

  • 135 - 143

PubMed ID

  • 15537663

Pubmed Central ID

  • 15537663

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

International Standard Serial Number (ISSN)

  • 0964-6906

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddi013

Language

  • eng