Catecholamine-O-Methyltransferase Polymorphisms Are Associated With Postoperative Pain Intensity

Objectives: Single nucleotide polymorphisms (SNPs) in the genes for catecholamine-O-methyltransferase (COMT), m-opioid receptor and GTP cyclohydrolase (GCH1) have been linked to acute and chronic pain states. COMT polymorphisms are associated with experimental pain sensitivity and a chronic pain state. No such association has been identified perioperatively. We carried out a prospective observational clinical trial to examine associations between these parameters and the development of postoperative pain in patients undergoing third molar (M3) extraction. Methods: Psychologic and clinical parameters were measured prospectively in a single homogeneous cohort of 100 patients undergoing M3 extraction. We genotyped the patients for SNPs within GCH1, COMT, and m-opioid receptor 1. Primary outcome was the occurrence of pain, 3 months after surgery. Other outcomes included pain measures in the early postoperative period and the week after surgery. Results: Seven patients (7/98; 7.1%) had persistent pain. Patients with and without persistent pain were similar in terms of perioperative demographic, psychological, and clinical parameters. The proportion who reported adequate postoperative analgesia was greater amongst those with the GG genotype for either rs4818 or rs6269 than those without (P<0.0001). The rare forms of COMT SNPs rs4818 and rs6269 were associated with postoperative pain of lesser intensity at rest (P=0.02, 0.03 respectively) and on movement (P=0.02, 0.01, respectively). The number of days until analgesia was not required during the first postoperative week was associated with GCH1 SNPs (rs8007267, P=0.05; rs3783641, P=0.01; rs10483636, P=0.002). Discussion: We report an early demonstration of a COMT SNP association with a clinically meaningful pain outcome after elective surgery.