Genetic polymorphisms have been shown to affect opioid requirement for pain relief. However, true genetic effect is often difficult to assess due to underlying pain conditions and placebo effects. The goal of this study was to understand how common polymorphisms affect opioid effects while controlling for these factors. A randomized, double-blind, placebo-controlled study was implemented to assess how opioid effects are modulated by COMT (rs6269, rs4633, rs4848, rs4680), OPRM1 (A118G), and OPRK1 (rs1051660, rs702764, rs16918875). One hundred and eight healthy subjects underwent experimental pain testing before and after morphine, butorphanol, and placebo (saline). Association analysis was performed between polymorphisms/haplotypes and opioid response, while correcting for race, gender, placebo effects, and multiple comparisons. Pressure pain was significantly associated with rs6269 and rs4633 following butorphanol. The AA genotype of rs4680 or A_T_C_A/ A_T_C_A (rs6269_rs4633_ rs4818_rs4680) diplotype of COMT, combined with the AG genotype of OPRM1 A118G, showed significantly increased pressure pain threshold from butorphanol. Opioid effects on pressure, ischemic, heat pain, and side effects were nominally associated with several SNPs and haplotypes. Effects were often present in one opioid but not the other. This indicates that these polymorphisms affect pain relief from opioids, and that their effects are opioid and pain modality specific.

基因多态性已被证明会影响缓解疼痛的阿片类药物的需求。然而，由于潜在的疼痛状况和安慰剂效应，真正的遗传效应通常很难评估。本研究的目的是了解常见的多态性如何影响阿片类药物的作用，同时控制这些因素。实施了一项随机、双盲、安慰剂对照研究，以评估COMT （rs6269、rs4633、rs4848、rs4680）、 OPRM1 （A118G）和OPRK1 （rs1051660、rs702764、rs16918875）如何调节阿片类药物的作用。一百零八名健康受试者在吗啡、布托啡诺和安慰剂（盐水）之前和之后接受了实验性疼痛测试。在多态性/单倍型和阿片类药物反应之间进行关联分析，同时校正种族、性别、安慰剂效应和多重比较。布托啡诺后压痛与 rs6269 和 rs4633 显着相关。 COMT的 rs4680 的 AA 基因型或 A_T_C_A/ A_T_C_A (rs6269_rs4633_ rs4818_rs4680) 二倍型与OPRM1 A118G 的 AG 基因型相结合，显示布托啡诺的压力痛阈值显着增加。阿片类药物对压力、缺血、热痛和副作用的影响名义上与多个 SNP 和单倍型相关。一种阿片类药物通常会产生效果，而另一种则不会。这表明这些多态性影响阿片类药物的疼痛缓解，并且它们的作用是阿片类药物和疼痛方式特异性的。