Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study.
Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study.
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DOI：
10.1097/fpc.0b013e328337f9ab
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发表时间：
2010-04
影响因子：
2.6
通讯作者：
Maixner W
中科院分区：
文献类型：
--
作者：
Tchivileva IE;Lim PF;Smith SB;Slade GD;Diatchenko L;McLean SA;Maixner W
儿茶酚氧位甲基转移酶(COMT)基因的三种常见单倍型与疼痛调制和慢性肌肉骨骼疼痛的风险有关，即颞下颌关节紊乱病(TMD)。编码较高酶活性的单倍型与较低的痛觉相关。啮齿动物研究表明，COMT抑制通过β2/3-肾上腺素能受体增加疼痛敏感性。我们假设，非选择性β肾上腺素能拮抗剂心得安将以一种依赖于受试者COMT双倍型的方式减轻TMD患者的临床和实验疼痛。符合TMD研究诊断标准的40名高加索女性参与者接受了COMT基因多态分型，并完成了一项随机、双盲、安慰剂对照、两期交叉的初步研究。每个周期包括一个基线评估周，然后是一个干预周(心得安或安慰剂)。比较了基线和干预周期间临床疼痛分级、心理状态以及对热和压力刺激的反应的变化。与安慰剂相比，心得安治疗期间报告疼痛强度分级降低的患者数量更多(p=0.014)。心得安显著降低综合疼痛指数(p=0.02)，但不降低其他临床和实验疼痛分级。当按COMT高活性单倍型分层时，在没有携带该单倍型的受试者中注意到心得安对疼痛感觉的有益影响，在杂合子中观察到的益处减少，在纯合子中没有观察到益处。COMT单倍型可作为心得安治疗结果的遗传预测因子，确定将受益于心得安治疗的TMD患者的亚组。
Three common haplotypes in the gene encoding catechol-O-methyltransferase (COMT) have been associated with pain modulation and the risk of developing chronic musculoskeletal pain, namely temporomandibular disorder (TMD). Haplotypes coding for higher enzymatic activity were correlated with lower pain perception. Rodent studies showed that COMT inhibition increases pain sensitivity via β2/3-adrenergic receptors. We hypothesized that the non-selective β-adrenergic antagonist propranolol will reduce clinical and experimental pain in TMD patients in a manner dependent on the subjects’ COMT diplotype. 40 female Caucasian participants meeting the Research Diagnostic Criteria for TMD were genotyped for COMT polymorphisms and completed a randomized, double–blind, placebo-controlled, two-period crossover pilot study. Each period consisted of a baseline assessment week followed by an intervention week (propranolol or placebo). Changes in clinical pain ratings, psychological status, and responses to heat and pressure stimuli between baseline and intervention weeks were compared across periods. The number of patients reporting a reduction in pain intensity rating was greater during propranolol treatment (p=0.014) compared with placebo. Propranolol significantly reduced a composite pain index (p=0.02) but did not decrease other clinical and experimental pain ratings. When stratified by the COMT high activity haplotype, a beneficial effect of propranolol on pain perception was noted in subjects not carrying this haplotype, a diminished benefit was observed in the heterozygotes, and no benefit was noted in the homozygotes. COMT haplotypes may serve as genetic predictors of propranolol treatment outcome, identifying a subgroup of TMD patients who will benefit from propranolol therapy.