Genetic basis for individual variations in pain perception and the development of a chronic pain condition |
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| Authors: | Diatchenko Luda Slade Gary D Nackley Andrea G Bhalang Konakporn Sigurdsson Asgeir Belfer Inna Goldman David Xu Ke Shabalina Svetlana A Shagin Dmitry Max Mitchell B Makarov Sergei S Maixner William |
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| Institution: | 1Comprehensive Center for Inflammatory Disorders, University of North Carolina at Chapel Hill, Columbia Street, CB#7455, Chapel Hill, NC 27599, USA,
2Australian Research Centre for Population Oral Health, University of Adelaide, Frome Road, SA 5005, Adelaide, Australia,
3Department of Oral Medicine, Chulalongkorn University, 254 Phyathai Road, Bangkok 10330, Thailand,
4Laboratory of Neurogenetics, NIAAA, NIH, 12420 Parklawn Drive, Park 5 Building, Rockville, MD 20852, USA,
5NCBI, NIH, 6404 Landon Lane, 8600 Rockville Pike, Bethesda, MD 20894, USA,
6Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia,
7NIDCR, NIH, Pain and Neurosensory Mechanisms Branch, Building 10, Room 3C-405, Bethesda, MD 20892-1258, USA and
8Attagene, Inc., 7030 Kit Creek Road, Research Triangle Park, NC 27560, USA |
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| Abstract: | Pain sensitivity varies substantially among humans. A significantpart of the human population develops chronic pain conditionsthat are characterized by heightened pain sensitivity. We identifiedthree genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase(COMT) that we designated as low pain sensitivity (LPS), averagepain sensitivity (APS) and high pain sensitivity (HPS). We showthat 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 experimentalpain. The presence of even a single LPS haplotype diminishes,by as much as 2.3 times, the risk of developing myogenous temporomandibularjoint disorder (TMD), a common musculoskeletal pain condition.The LPS haplotype produces much higher levels of COMT enzymaticactivity when compared with the APS or HPS haplotypes. Inhibitionof 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 humansthat inversely correlates with pain sensitivity and the riskof developing TMD. |
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