Natural variation in the μ-opioid gene OPRM1 predicts increased pain on third day after thoracotomy

Objectives: The mechanism whereby acute postsurgical pain can persist and become chronic remains unknown. Thoracotomy is a common procedure with a high incidence of long-term pain for which acute postsurgical pain is an established risk factor. Therefore, the genetic basis of elevations in acute postsurgical pain after thoracotomy was investigated. Methods: A cohort of thoracotomy patients participating in an ongoing trial of outcomes after cancer were enrolled. A standard combined general and epidural anesthetic and surgical approach were used. All patients received a standardized postoperative epidural analgesia regimen. Postoperatively, pain scores were determined and blood was collected for genotyping. Our a priori hypothesis was that variability of genes involved in nociception and analgesic therapy would predict pain score 3 of 10 on the third postoperative day. Results: Ninety patients with pain and genotyping data on postoperative day 3 were examined. We found no association between markers in COMT, COX1, COX2, and TRPV1 and postoperative pain. We demonstrated several statistically significant associations with 4 single nucleotide polymorphism markers in OPRM1 (odds ratio, 95% confidence intervals): rs634479 (0.4, 0.17, 0.97), rs499796 (0.35, 0.13, 0.92), rs548646 (0.47, 0.23, 0.97), and rs679987 (0.1, 0.01, 0.84). From these, we inferred 2 haplotype blocks in OPRM1 where both had a frequency of 9% and P=0.03 and 0.04. Previously published functional single nucleotide polymorphisms in OPRM1 and COMT were not associated with increased pain on the third postoperative day. Discussion: We identified previously unpublished haplotypes of the OPRM1 receptor that predicted increases in self-reported pain on the third postoperative day after thoracotomy. These findings require replication and further refinement before their impact on patient care can be determined.