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


CONCLUSIONS
We identified previously unpublished haplotypes of the OPRM1 receptor that predicted increases in self-reported pain on the third postoperative day after thoracotomy.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.
Department of Anesthesiology and Critical Care, Division of Pulmonary and Critical Care, University of Pennsylvania, PA 19104, USA. ochrocha@uphs.upenn.edu
Edward Andrew
EA
Ochroch
Anil
A
Vachani
Allan
A
Gottschalk
Peter A
PA
Kanetsky
D000368:Aged; D000700:Analgesics / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000235:genetics; D016009:Chi-Square Distribution; D015331:Cohort Studies; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D017450:Receptors, Opioid, mu / Q000235:genetics*; D050916:TRPV Cation Channels / Q000235:genetics; D013908:Thoracotomy / Q000009:adverse effects*
D000700:Analgesics; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D002394:Catechol O-Methyltransferase