How Much Oxycodone Is Needed for Adequate Analgesia After Breast Cancer Surgery: Effect of the OPRM1 118A>G Polymorphism

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>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>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. Intravenous 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>G polymorphism was genotyped using the Sequenom MassARRAY (Sequenom, San Diego, CA). The association between this variant and the pain phenotypes was tested using linear regression. The 118A>G variant was associated significantly with the amount of oxycodone requested for adequate analgesia (P = .003, β = .016). Collectively, oxycodone consumption was highest in individuals having the GG genotype (.16 mg/kg), lowest for those with the AA genotype (.12 mg/kg), and moderate for those having the AG genotype (.13 mg/kg). Furthermore, the G allele was associated with higher postoperative baseline pain ratings (P = .001, β = .44). No evidence of association with other pain phenotypes examined was observed. PerspectiveThis study demonstrates that the OPRM1 118A>G polymorphism was associated with the amount of oxycodone required in the immediate postoperative period. Although a significant factor for determining oxycodone requirement, the 118A>G polymorphism alone explained less than 1% of the variance. No association was found between 118A>G and experimental pain.