Genetic basis for individual variations in pain perception and the development of a chronic pain condition
Genetic basis for individual variations in pain perception and the development of a chronic pain condition
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DOI：
10.1093/hmg/ddi013
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发表时间：
2005-01-01
影响因子：
3.5
通讯作者：
Maixner, W
中科院分区：
文献类型：
--
作者：
Diatchenko, L;Slade, GD;Maixner, W
疼痛的敏感性在人类之间有很大的差异。很大一部分人患有以疼痛敏感性升高为特征的慢性疼痛病症。我们确定了三种编码儿茶酚胺-O-甲基转移酶（COMT）的基因的遗传变体（单倍型），我们将其命名为低疼痛敏感性（LPS），平均疼痛敏感性（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，这些单倍型的五种组合与实验疼痛敏感性的变化密切相关（P=0.0004）。即使是一个单一的LPS单倍型的存在减少，多达2.3倍，发展肌源性颞下颌关节紊乱病（TMD），一种常见的肌肉骨骼疼痛的条件的风险。当与APS或HPS单倍型相比时，LPS单倍型产生高得多的水平的COMT酶活性。在大鼠中抑制COMT导致疼痛敏感性的显著增加。因此，COMT活性显著影响疼痛敏感性，并且三种主要单倍型决定了人类中与疼痛敏感性和发展TMD的风险负相关的COMT活性。
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.