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

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

Stephan G Frangakis  1 , Mark MacEachern  2 , T Adam Akbar  3 , Christian Bolton  1 , Victor Lin  4 , Albert V Smith  5 , Chad M Brummett  6 , Mark C Bicket  6
Affiliations
Meta-Analysis

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

Stephan G Frangakis et al. Anesthesiology. .

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.

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Conflict of interest statement

Competing Interests

Dr. Brummett is a consultant for Heron Therapeutics (San Diego, California) and Vertex Pharmaceuticals (Boston, Massachusetts) and has received one-time consultancy fees from the Benter Foundation (Pittsburgh, Pennsylvania) and Alosa Health (Boston, Massachusetts). He also provides expert witness consultation. None of these disclosures are relevant to the work presented. Dr. Bicket has received grants from the National Institutes of Health (Bethesda, Maryland), grants from the Centers for Disease Control and Prevention (Atlanta, Georgia), grants from the Michigan Department of Health and Human Services (Lansing, Michigan), grants from the Arnold Foundation (Washington, D.C.), and grants from the Patient-Centered Outcomes Research Institute (Washington, D.C.) outside the submitted work. The other authors declare no competing interests.

Comment in

References

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