Published in J Pain. 2014 Sep 16. pii: S1526-5900(14)00911-0
Authors: Cajanus K et al
Abstract
Most clinically used opioids are mu-opioid receptor agonists. Therefore, genetic variation of the OPRM1 gene that encodes the mu-opioid receptor is of great interest for understanding pain management. A polymorphism 118A greater than G (rs1799971) within the OPRM1 gene results in a missense mutation and affects the function of the receptor.
We studied the association between the 118A greater than G polymorphism and oxycodone analgesia and pain sensitivity in 1,000 women undergoing breast cancer surgery.
Preoperatively, experimental cold and heat pain sensitivities were tested. Postoperative pain was assessed at rest and during motion. I.v. oxycodone analgesia was titrated first by a research nurse and on the ward using a patient-controlled analgesia device.
The primary endpoint was the amount of oxycodone needed for the first state of adequate analgesia. For each patient, the 118A great than G polymorphism was genotyped using Sequenom MassArray. The association between this variant and the pain phenotypes was tested using linear regression. The 118A greater than G variant was associated significantly with the amount of oxycodone requested for adequate analgesia (P=0.001, β=0.016).
Collectively, oxycodone consumption was highest in individuals having the GG genotype (0.16 mgkg-1), lowest for the AA genotype-group (0.12 mg kg-¹), and moderate for the AG genotype-group (0.13 mg kg-¹). Furthermore, the G allele was associated with higher postoperative baseline pain ratings (P=0.001, β=0.44). No evidence of association with other pain phenotypes examined was observed.
PERSPECTIVE:
This study demonstrates that the OPRM1 118 A greater than G polymorphism associated with the amount of oxycodone required in the immediate post-operative period. Although a significant factor for determining oxycodone requirement, the 118A greater than G polymorphism alone explained less than 1% of the variance. No association was found between 118A greater than G and experimental pain.