title: Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study.
abstract: The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental pain model in 40 healthy participants aged 20-65. Seventeen different single nucleotide polymorphisms in different genes (OPRM, OPRK, OPRD and COMT) were included in the analysis. Experimental pain tests included thermal skin stimulation, mechanical muscle and bone stimulation and mechanical, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p < 0.015). Additionally, carriers of the C allele (CC/CT) of OPRK rs6473799 reported a 30.4% higher mechanical visceral pain tolerance threshold than non-carriers (TT; p < 0.019). For the other polymorphisms and stimulations, no associations were found (all p > 0.05). In conclusion, COMT rs4680 and OPRK rs6473799 polymorphisms seem to be associated with pain sensitivity. Thus, the findings support a possible genetic influence on pain sensitivity.
authors.affiliation: Department of Gastroenterology and Hepatology, Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.|Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lecia Møller
authors.initials: LM
authors.lastname: Nielsen
authors.affiliation: Department of Gastroenterology and Hepatology, Mech-Sense, Aalborg University Hospital, Aalborg, Denmark. aneso@rn.dk.|Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. aneso@rn.dk.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. aneso@rn.dk.
authors.forename: Anne Estrup
authors.initials: AE
authors.lastname: Olesen
authors.affiliation: Interstitial Lung Disease Unit, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London, UK.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Sato
authors.affiliation: Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lona Louring
authors.initials: LL
authors.lastname: Christrup
authors.affiliation: Department of Gastroenterology and Hepatology, Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D003718:Denmark; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010147:Pain Measurement; D017288:Pain Threshold; D020641:Polymorphism, Single Nucleotide; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000235:genetics* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D008024:Ligands; C529706:OPRD1 protein, human; C515653:OPRK1 protein, human; C485764:OPRM1 protein, human; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase