Genetic basis for individual variations in pain perception and the development of a chronic pain condition.
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.
Diatchenko
Luda
L
Comprehensive Center for Inflammatory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. lbdiatch@email.unc.edu
Slade
Gary D
GD
Nackley
Andrea G
AG
Bhalang
Konakporn
K
Sigurdsson
Asgeir
A
Belfer
Inna
I
Goldman
David
D
Xu
Ke
K
Shabalina
Svetlana A
SA
Shagin
Dmitry
D
Max
Mitchell B
MB
Makarov
Sergei S
SS
Maixner
William
W
D000293:Adolescent; D000328:Adult; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002908:Chronic Disease; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D010146:Pain / Q000150:complications / Q000235:genetics*; D051381:Rats; D012307:Risk Factors; D013705:Temporomandibular Joint Disorders / Q000209:etiology
D002394:Catechol O-Methyltransferase