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

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          Abstract

          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.

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          Author and article information

          Journal
          Hum Mol Genet
          Human molecular genetics
          Oxford University Press (OUP)
          0964-6906
          0964-6906
          Jan 01 2005
          : 14
          : 1
          Affiliations
          [1 ] Comprehensive Center for Inflammatory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. lbdiatch@email.unc.edu
          Article
          ddi013
          10.1093/hmg/ddi013
          15537663
          9142da43-c337-4a02-ada1-f59fa19499ca
          History

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