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
Comprehensive Center for Inflammatory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Hum Mol Genet. 2005 Jan 1;14(1):135-43. doi: 10.1093/hmg/ddi013. Epub 2004 Nov 10.
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.
人类的疼痛敏感性差异很大。很大一部分人会患上慢性疼痛疾病，其特征是疼痛敏感性增强。我们鉴定出了编码儿茶酚-O-甲基转移酶（COMT）的基因的三种基因变体（单倍型），我们将其分别命名为低疼痛敏感性（LPS）、中等疼痛敏感性（APS）和高疼痛敏感性（HPS）。我们发现这些单倍型涵盖了96%的人群，并且这些单倍型的五种组合与实验性疼痛敏感性的变化密切相关（P = 0.0004）。即使仅存在一个LPS单倍型，也能将发生肌源性颞下颌关节紊乱病（TMD，一种常见的肌肉骨骼疼痛疾病）的风险降低多达2.3倍。与APS或HPS单倍型相比，LPS单倍型产生的COMT酶活性水平要高得多。在大鼠中抑制COMT会导致疼痛敏感性大幅增加。因此，COMT活性会显著影响疼痛敏感性，这三种主要单倍型决定了人类的COMT活性，而COMT活性与疼痛敏感性以及患TMD的风险呈负相关。
