title: 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 whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral PTT (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 single-nucleotide polymorphisms (SNPs) rs589046 (P < 0.0001) and rs563649 (P < 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.
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.|Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Olesen
authors.affiliation: Interstitial Lung Disease Unit, Royal Brompton Hospital & National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Sato
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.|Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lecia M
authors.initials: LM
authors.lastname: Nielsen
authors.affiliation: Novo Nordisk A/S, Copenhagen, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Staahl
authors.affiliation: Interstitial Lung Disease Unit, Royal Brompton Hospital & National Heart and Lung Institute, Imperial College London, London, UK.|Department of Palliative Medicine, Royal Marsden Hospital, London, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Droney
authors.affiliation: Interstitial Lung Disease Unit, Royal Brompton Hospital & National Heart and Lung Institute, Imperial College London, London, UK.|Department of Palliative Medicine, Royal Marsden Hospital, London, UK.
authors.forename: Sophy
authors.initials: S
authors.lastname: Gretton
authors.affiliation: Interstitial Lung Disease Unit, Royal Brompton Hospital & National Heart and Lung Institute, Imperial College London, London, UK.|Department of Palliative Medicine, Royal Marsden Hospital, London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Branford
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Asbjørn M
authors.initials: AM
authors.lastname: Drewes
authors.affiliation: SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.affiliation: Department of Palliative Medicine, Royal Marsden Hospital, London, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Riley
authors.affiliation: Interstitial Lung Disease Unit, Royal Brompton Hospital & National Heart and Lung Institute, Imperial College London, London, UK.|Department of Palliative Medicine, Royal Marsden Hospital, London, UK.
authors.forename: Joy
authors.initials: J
authors.lastname: Ross
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D004247:DNA / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006358:Hot Temperature; D006801:Humans; D008297:Male; D010098:Oxycodone / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000235:genetics*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011312:Pressure; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004247:DNA; D010098:Oxycodone
keywords: OPRD1; OPRK1; OPRM1; analgesia; experimental pain; oxycodone