Association of μ-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty

Background: Morphine consumption after a given surgical procedure can vary considerably. Studies show that single nucleotide polymorphism involving the nucleotide position 118 at exon 1 of the mu-opioid receptor gene (OPRM1) may play a role in mediating the effects of opioids. This study was performed to correlate the A118G polymorphism at OPRM1 with morphine consumption in patients undergoing total knee arthroplasty. Methods: Post-operative pain was relieved by patient-controlled analgesia (PCA). The analgesic effect was evaluated using a visual analogue scale. Side-effects, such as sedation, nausea and vomiting, and pruritus, were recorded systematically. The genotypes were determined by sequencing polymerase chain reaction-amplified DNA. The differences in demographics and consumed morphine from the PCA device between the different genotypes were tested using one-way analysis of variance. The prevalence of side-effects from morphine and sex distribution were compared using the Kruskal-Wallis test. Results: One hundred and forty-seven patients were included in the study. Twenty-seven patients who required rescue analgesia were excluded; these patients did not differ demographically or genetically from the 120 who completed the study. Of the latter, 74 were A118 homozygous (AA), 33 were heterozygous (AG) and 13 were G118 homozygous (GG). Group GG consumed significantly more morphine (40.4 +/- 22.0 mg) than group AA (25.3 +/- 15.5 mg) and group AG (25.6 +/- 11.7 mg) during the first 48 h post-operatively. The groups did not differ with respect to reported pain, age, sex, weight and adverse effects. Conclusions: G118 homozygotes have a poorer response to morphine for post-operative pain control than A118 homozygotes or heterozygotes. The genotype may thus influence the post-operative response to pain and cause differences in the amounts of analgesic consumed by patients after total knee arthroplasty.