The Genetic Influences on Oxycodone Response Characteristics in Human Experimental Pain

Abstract

Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate if genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1 respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multi-modal, multi-tissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (n=37), muscle pressure pain tolerance threshold (n=31), mechanical visceral pain tolerance threshold (n=43), and thermal visceral pain tolerance threshold (n=41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 SNPs rs589046 (P&lt;0.0001) and rs563649 (P&lt;0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P=0.015), rs1799971 (P=0.045), rs9479757 (P=0.009) and rs533586 (P=0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold however one OPRD1 rs419335 reached significance (P=0.015). Another OPRD1 SNP rs2234918 (P=0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs, therefore variation in opioid receptor genes may partly explain responder characteristics to oxycodone. This article is protected by copyright. All rights reserved.</p