{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T14:15:24Z","timestamp":1786198524860,"version":"build-2736575974"},"reference-count":39,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["U01-DE024169"],"award-info":[{"award-number":["U01-DE024169"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:p>Propranolol is a nonselective \u03b2-adrenergic receptor antagonist that is efficacious in reducing facial pain. There is evidence that its analgesic efficacy might be modified by variants of the catechol-O-methyltransferase ( COMT) gene. We tested the hypothesis in a subset of 143 non-Hispanic Whites from a randomized controlled trial of patients with painful temporomandibular disorder (TMD). Patients were genotyped for rs4680, a single nucleotide polymorphism of COMT, and randomly allocated to either propranolol 60 mg twice daily or placebo. During the 9-wk follow-up period, patients recorded daily ratings of facial pain intensity and duration; the product was computed as an index of facial pain. Postbaseline change in the index at week 9 (the primary endpoint) was analyzed as a continuous variable and dichotomized at thresholds of \u226530% and \u226550% reduction. Mixed models for repeated measures tested for the genotype \u00d7 treatment group interaction and estimated means, odds ratios (ORs), and 95% confidence limits (95% CLs) of efficacy within COMT genotypes assuming an additive genetic model. In secondary analysis, the cumulative response curves were plotted for dichotomized reductions ranging from \u226520% to \u226570%, and genotype differences in area under the curve percentages (%AUC) were calculated to signify efficacy. Mean index reduction did not differ significantly ( P = 0.277) according to genotype, whereas the dichotomized \u226530% reduction revealed greater efficacy among G:G homozygotes (OR = 10.9, 95%CL = 2.4, 50.7) than among A:A homozygotes (OR = 0.8, 95%CL = 0.2, 3.2) with statistically significant interaction ( P = 0.035). Cumulative response curves confirmed greater ( P = 0.003) efficacy for G:G homozygotes (%AUC difference = 43.7, 95%CL = 15.4, 72.1) than for A:A homozygotes (%AUC difference = 6.5, 95%CL = -30.2, 43.2). The observed antagonistic effect of the A allele on propranolol\u2019s efficacy was opposite the synergistic effect hypothesized a priori. This unexpected result highlights the need for better knowledge of COMT\u2019s role in pain pathogenesis if the gene is to be used for precision-medicine treatment of TMD (ClinicalTrials.gov NCT02437383).<\/jats:p>","DOI":"10.1177\/0022034520962733","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T08:14:47Z","timestamp":1602144887000},"page":"163-170","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["<i>COMT<\/i>\n                    Genotype and Efficacy of Propranolol for TMD Pain: A Randomized Trial"],"prefix":"10.1177","volume":"100","author":[{"given":"G.D.","family":"Slade","sequence":"first","affiliation":[{"name":"Center for Pain Research and Innovation, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"name":"Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina at 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