title: Gender, variation in opioid receptor genes and sensitivity to experimental pain.
abstract: BACKGROUND
  Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included.
  
  
  RESULTS
  Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain.
  
  
  CONCLUSIONS
  This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions.
authors.affiliation: Clinical Genomics group, Imperial College London, London, UK. h.sato@imperial.ac.uk
authors.forename: Hiroe
authors.initials: H
authors.lastname: Sato
authors.forename: Joanne
authors.initials: J
authors.lastname: Droney
authors.forename: Joy
authors.initials: J
authors.lastname: Ross
authors.forename: Anne Estrup
authors.initials: AE
authors.lastname: Olesen
authors.forename: Camilla
authors.initials: C
authors.lastname: Staahl
authors.forename: Trine
authors.initials: T
authors.lastname: Andresen
authors.forename: Ruth
authors.initials: R
authors.lastname: Branford
authors.forename: Julia
authors.initials: J
authors.lastname: Riley
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D000375:Aging / Q000473:pathology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009132:Muscles / Q000473:pathology; D010146:Pain / Q000235:genetics*; D017288:Pain Threshold; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011957:Receptors, Opioid / Q000235:genetics*; D012044:Regression Analysis; D012727:Sex Characteristics; D014781:Viscera / Q000473:pathology; D055815:Young Adult
chemical_list: D011957:Receptors, Opioid