Belfer Inna, Dai Feng, Kehlet Henrik, Finelli Peter, Qin Li, Bittner Reinhard, Aasvang Eske K
Departments of Anesthesiology and Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA Yale Center for Analytical Sciences, Yale University, New Haven, CT, USA Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark Department of Surgery, Marienhospital Stuttgart, Stuttgart, Germany.
Pain. 2015 Feb;156(2):273-279. doi: 10.1097/01.j.pain.0000460307.48701.b0.
Persistent postoperative pain is a well-established clinical problem with potential severe personal and socioeconomic implications. The prevalence of persistent pain varies across surgery types. Severe persistent pain and related impairment occur in 5% to 10% of patients after groin hernia repair. The substantial interindividual variability in pain-related phenotypes within each surgery type cannot be explained by environmental factors alone, suggesting that genetic variation may play a role. We investigated the contribution of COMT and GCH1 to persistent postherniotomy pain (PPP)-related functional impairment. Prospective data from 429 Caucasian male patients with hernia were collected. Three COMT and 2 GCH1 tagging single-nucleotide polymorphisms (SNPs) were genotyped and analyzed for association with PPP-related activity impairment at 6 months after herniotomy. Fifty-five (12.8%) patients had moderate-to-severe pain-related activity impairment 6 months postoperatively as measured by Activity Assessment Scale (≥8.3). Patients with the G allele of COMT SNP rs6269 and C allele of COMT SNP rs4633 had less impairment (P = 0.03 and 0.01, respectively); in addition, the COMT haplotype GCG was associated with less impairment. For GCH1, the A allele of SNP rs3783641, T allele of rs8007267, and AT haplotype showed a protective effect trend (although nonsignificant; P = 0.08, 0.06, and 0.08, respectively). A prediction model of substantial PPP-related activity impairment, combining COMT and GCH1 SNPs with clinical, psychophysical, and psychological risk factors, had a "good" (0.8 < area under curve < 0.9) discriminatory power. These data suggest that functional variations in COMT and GCH1 combined with clinical factors are predictive of PPP-related impairment after groin herniotomy.
术后持续性疼痛是一个已被充分认识的临床问题，具有潜在的严重个人和社会经济影响。持续性疼痛的患病率因手术类型而异。腹股沟疝修补术后5%至10%的患者会出现严重的持续性疼痛及相关功能障碍。每种手术类型中疼痛相关表型的个体间差异很大，仅环境因素无法解释这种差异，这表明基因变异可能起作用。我们研究了儿茶酚-O-甲基转移酶（COMT）和蝶呤-4α-羧化酶1（GCH1）对疝修补术后持续性疼痛（PPP）相关功能障碍的影响。收集了429例白种人男性疝患者的前瞻性数据。对3个COMT和2个GCH1标签单核苷酸多态性（SNP）进行基因分型，并分析其与疝修补术后6个月时PPP相关活动障碍的相关性。根据活动评估量表（≥8.3）测量，55例（12.8%）患者术后6个月有中度至重度疼痛相关活动障碍。COMT SNP rs6269的G等位基因和COMT SNP rs4633的C等位基因患者的功能障碍较少（P分别为0.03和0.01）；此外，COMT单倍型GCG与较少的功能障碍相关。对于GCH1，SNP rs3783641的A等位基因、rs8007267的T等位基因和AT单倍型显示出保护作用趋势（尽管无统计学意义；P分别为0.08、0.06和0.08）。一个结合COMT和GCH1 SNPs与临床、心理物理和心理风险因素的PPP相关活动严重障碍预测模型具有“良好”（0.8<曲线下面积<0.9）的辨别力。这些数据表明，COMT和GCH1的功能变异与临床因素相结合可预测腹股沟疝修补术后PPP相关功能障碍。
