阿片类药物用于乳腺癌手术后镇痛的适宜剂量：OPRM1 118A>G 多态性的影响。

How much oxycodone is needed for adequate analgesia after breast cancer surgery: effect of the OPRM1 118A>G polymorphism.

机构信息

Department of Anaesthesia, Intensive Care Medicine, Emergency Medicine and Pain Medicine, Helsinki University Central Hospital, Helsinki, Finland.

出版信息

J Pain. 2014 Dec;15(12):1248-56. doi: 10.1016/j.jpain.2014.09.002.

DOI:10.1016/j.jpain.2014.09.002

PMID:25239082

Abstract

UNLABELLED

Most clinically used opioids are mu-opioid receptor agonists. Therefore, genetic variation of the OPRM1 gene that encodes the mu-opioid receptor is of great interest for understanding pain management. A polymorphism 118A>G (rs1799971) within the OPRM1 gene results in a missense mutation and affects the function of the receptor. We studied the association between the 118A>G polymorphism and oxycodone analgesia and pain sensitivity in 1,000 women undergoing breast cancer surgery. Preoperatively, experimental cold and heat pain sensitivities were tested. Postoperative pain was assessed at rest and during motion. Intravenous oxycodone analgesia was titrated first by a research nurse and on the ward using a patient-controlled analgesia device. The primary endpoint was the amount of oxycodone needed for the first state of adequate analgesia. For each patient, the 118A>G polymorphism was genotyped using the Sequenom MassARRAY (Sequenom, San Diego, CA). The association between this variant and the pain phenotypes was tested using linear regression. The 118A>G variant was associated significantly with the amount of oxycodone requested for adequate analgesia (P = .003, β = .016). Collectively, oxycodone consumption was highest in individuals having the GG genotype (.16 mg/kg), lowest for those with the AA genotype (.12 mg/kg), and moderate for those having the AG genotype (.13 mg/kg). Furthermore, the G allele was associated with higher postoperative baseline pain ratings (P = .001, β = .44). No evidence of association with other pain phenotypes examined was observed.

PERSPECTIVE

This study demonstrates that the OPRM1 118A>G polymorphism was associated with the amount of oxycodone required in the immediate postoperative period. Although a significant factor for determining oxycodone requirement, the 118A>G polymorphism alone explained less than 1% of the variance. No association was found between 118A>G and experimental pain

摘要

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大多数临床上使用的阿片类药物都是μ-阿片受体激动剂。因此，编码μ-阿片受体的 OPRM1 基因的遗传变异对于理解疼痛管理具有重要意义。OPRM1 基因内的 118A>G（rs1799971）多态性导致错义突变并影响受体的功能。我们研究了 1000 名接受乳腺癌手术的女性中 OPRM1 基因 118A>G 多态性与羟考酮镇痛和疼痛敏感性之间的关系。术前，测试了实验性冷和热痛觉敏感性。术后休息和运动时评估疼痛。静脉注射羟考酮镇痛首先由研究护士通过患者自控镇痛装置滴定。主要终点是达到足够镇痛的第一个状态所需的羟考酮量。对于每个患者，使用 Sequenom MassARRAY（Sequenom，圣地亚哥，CA）对 118A>G 多态性进行基因分型。使用线性回归测试该变体与疼痛表型之间的关联。118A>G 变体与达到足够镇痛所需的羟考酮量显著相关（P=0.003，β=0.016）。总体而言，具有 GG 基因型的个体羟考酮消耗量最高（0.16mg/kg），AA 基因型的个体最低（0.12mg/kg），AG 基因型的个体居中（0.13mg/kg）。此外，G 等位基因与术后基线疼痛评分较高相关（P=0.001，β=0.44）。未观察到与其他研究的疼痛表型有关的证据。