遗传变异与术后疼痛的关联：系统评价和荟萃分析。

Association of Genetic Variants with Postsurgical Pain: A Systematic Review and Meta-analyses.

机构信息

Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan.

Taubman Health Sciences Library, University of Michigan, Ann Arbor, Michigan.

出版信息

Anesthesiology. 2023 Dec 1;139(6):827-839. doi: 10.1097/ALN.0000000000004677.

DOI:10.1097/ALN.0000000000004677

PMID:37774411

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10859728/

Abstract

BACKGROUND

Postsurgical pain is a key component of surgical recovery. However, the genetic drivers of postsurgical pain remain unclear. A broad review and meta-analyses of variants of interest will help investigators understand the potential effects of genetic variation.

METHODS

This article is a systematic review of genetic variants associated with postsurgical pain in humans, assessing association with postsurgical pain scores and opioid use in both acute (0 to 48 h postoperatively) and chronic (at least 3 months postoperatively) settings. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from 2000 to 2022 for studies using search terms related to genetic variants and postsurgical pain in humans. English-language studies in adult patients examining associations of one or more genetic variants with postsurgical pain were included. The primary outcome was association of genetic variants with either acute or chronic postsurgical pain. Pain was measured by patient-reported pain score or analgesic or opioid consumption.

RESULTS

A total of 163 studies were included, evaluating 129 unique genes and 594 unique genetic variants. Many of the reported significant associations fail to be replicated in other studies. Meta-analyses were performed for seven variants for which there was sufficient data (OPRM1 rs1799971; COMT rs4680, rs4818, rs4633, and rs6269; and ABCB1 rs1045642 and rs2032582). Only two variants were associated with small differences in postsurgical pain: OPRM1 rs1799971 (for acute postsurgical opioid use standard mean difference = 0.25; 95% CI, 0.16 to 0.35; cohort size, 8,227; acute postsurgical pain score standard mean difference = 0.20; 95% CI, 0.09 to 0.31; cohort size, 4,619) and COMT rs4680 (chronic postsurgical pain score standard mean difference = 0.26; 95% CI, 0.08 to 0.44; cohort size, 1,726).

CONCLUSIONS

Despite much published data, only two alleles have a small association with postsurgical pain. Small sample sizes, potential confounding variables, and inconsistent findings underscore the need to examine larger cohorts with consistent outcome measures.

摘要

背景

术后疼痛是手术恢复的一个关键组成部分。然而，术后疼痛的遗传驱动因素仍不清楚。对感兴趣的变体进行广泛的综述和荟萃分析将帮助研究人员了解遗传变异的潜在影响。

方法

这是一篇系统综述，综述了与人类术后疼痛相关的遗传变异，评估了这些变异与术后疼痛评分和阿片类药物使用的相关性，包括急性（术后 0 至 48 小时）和慢性（术后至少 3 个月）两个阶段。从 2000 年至 2022 年，我们通过与人类遗传变异和术后疼痛相关的检索词，在 PubMed、Embase 和 Cochrane 对照试验中心注册库中搜索了相关研究。纳入了研究一个或多个遗传变异与术后疼痛相关性的成年患者的英语研究。主要结局是遗传变异与急性或慢性术后疼痛的相关性。疼痛通过患者报告的疼痛评分或镇痛药或阿片类药物的使用来衡量。

结果

共纳入 163 项研究，评估了 129 个独特基因和 594 个独特的遗传变异。许多报告的显著相关性在其他研究中未能得到复制。对有足够数据的七个变体进行了荟萃分析（OPRM1 rs1799971；COMT rs4680、rs4818、rs4633 和 rs6269；以及 ABCB1 rs1045642 和 rs2032582）。只有两个变体与术后疼痛的微小差异相关：OPRM1 rs1799971（用于急性术后阿片类药物使用的标准均数差=0.25；95%置信区间，0.16 至 0.35；队列大小，8227；急性术后疼痛评分的标准均数差=0.20；95%置信区间，0.09 至 0.31；队列大小，4619）和 COMT rs4680（慢性术后疼痛评分的标准均数差=0.26；95%置信区间，0.08 至 0.44；队列大小，1726）。