Integrative Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
J Pain. 2023 Sep;24(9):1721-1730. doi: 10.1016/j.jpain.2023.05.005. Epub 2023 May 13.
Catechol-O-methyltransferase (COMT) is the major enzyme involved in the catabolism of dopamine, a neurotransmitter in the brain's reward system. The common COMT polymorphism Val158Met (rs4680 G>A) modulates pain response to opioids through a reward-motivated mechanism; however, its role in nonpharmacological pain medicine has not been clinically characterized. We genotyped 325 participants from a randomized controlled trial of cancer survivors with chronic musculoskeletal pain. We found that carrying methionine at position 158 (158Met) of COMT, encoded by the A allele, significantly increased the analgesic response to electroacupuncture (74% vs 50%; odds ratio [OR]: 2.79; 95% confidence interval [CI]: 1.31, 6.05; P < .01), but not to auricular acupuncture (68% vs 60%; OR: 1.43; 95% CI: .65, 3.12; P = .37) or usual care (24% vs 18%; OR: 1.46; 95% CI: .38, 7.24; P = .61) compared to Val/Val. These findings raise the possibility that COMT Val158Met might be an important predictor of analgesic response to electroacupuncture, providing novel insights into precision nonpharmacologic pain management tailored to individual genetic backgrounds. PERSPECTIVE: This work suggests the modulating effects of the polymorphism in COMT Val158Met on the response to acupuncture. Further research needs to validate these findings, increase the mechanistic understanding of acupuncture, and guide further development of acupuncture as a precision pain management strategy.
儿茶酚-O-甲基转移酶（COMT）是大脑奖励系统中多巴胺代谢的主要酶。常见的 COMT 多态性 Val158Met（rs4680 G>A）通过奖励驱动机制调节阿片类药物的疼痛反应；然而，其在非药物性疼痛医学中的作用尚未在临床上得到描述。我们对来自癌症幸存者慢性肌肉骨骼疼痛的随机对照试验的 325 名参与者进行了基因分型。我们发现，COMT 第 158 位（158Met）位置携带甲硫氨酸（由 A 等位基因编码），显著增加了电针对疼痛的缓解作用（74%对 50%；优势比[OR]：2.79；95%置信区间[CI]：1.31，6.05；P<.01），但对耳针（68%对 60%；OR：1.43；95% CI：.65，3.12；P=.37）或常规护理（24%对 18%；OR：1.46；95% CI：.38，7.24；P=.61）没有影响。与 Val/Val 相比，这些发现增加了 COMT Val158Met 可能是电针对疼痛缓解反应的重要预测因子的可能性，为针对个体遗传背景的精准非药物性疼痛管理提供了新的见解。观点：这项工作表明 COMT Val158Met 多态性对针刺反应的调节作用。需要进一步的研究来验证这些发现，增加对针刺的机制理解，并指导进一步开发针刺作为一种精准疼痛管理策略。
