title: Effect of catechol-o-methyltransferase-gene (COMT) variants on experimental and acute postoperative pain in 1,000 women undergoing surgery for breast cancer.
abstract: BACKGROUND
  Catechol-O-methyltransferase (COMT) metabolizes catecholamines in different tissues. Polymorphisms in COMT gene can attenuate COMT activity and increase sensitivity to pain. Human studies exploring the effect of COMT polymorphisms on pain sensitivity have mostly included small, heterogeneous samples and have ignored several important single nucleotide polymorphisms (SNPs). This study examines the effect of COMT polymorphisms on experimental and postoperative pain phenotypes in a large ethnically homogeneous female patient cohort.
  
  
  METHODS
  Intensity of cold (+2-4°C) and heat (+48°C) pain and tolerance to cold pain were assessed in 1,000 patients scheduled for breast cancer surgery. Acute postoperative pain and oxycodone requirements were recorded. Twenty-two COMT SNPs were genotyped and their association with six pain phenotypes analyzed with linear regression.
  
  
  RESULTS
  There was no association between any of the tested pain phenotypes and SNP rs4680. The strongest association signals were seen between rs165774 and heat pain intensity as well as rs887200 and cold pain intensity. In both cases, minor allele carriers reported less pain. Neither of these results remained significant after strict multiple testing corrections. When analyzed further, the effect of rs887200 was, however, shown to be significant and consistent throughout the cold pressure test. No evidence of association between the SNPs and postoperative oxycodone consumption was found.
  
  
  CONCLUSIONS
  SNPs rs887200 and rs165774 located in the untranslated regions of the gene had the strongest effects on pain sensitivity. Their effect on pain is described here for the first time. These results should be confirmed in further studies and the potential functional mechanisms of the variants studied.
authors.affiliation: * Student, Department of Anaesthesia, Intensive Care Medicine, Emergency Medicine and Pain Medicine, Helsinki University Central Hospital, Helsinki, Finland, and Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. † Senior Researcher, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, and Folkhälsan Institute of Genetics, Folkhälsan Research Center. ‡ Student, ‖ Professor, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, and Department of Chronic Disease Prevention, National Institute for Health and Welfare. § Professor, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. # Professor, Department of Anaesthesia, Intensive Care Medicine, Emergency Medicine and Pain Medicine, Helsinki University Central Hospital.
authors.forename: Oleg
authors.initials: O
authors.lastname: Kambur
authors.forename: Mari A
authors.initials: MA
authors.lastname: Kaunisto
authors.forename: Emmi
authors.initials: E
authors.lastname: Tikkanen
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Eija A
authors.initials: EA
authors.lastname: Kalso
mesh_terms: D059787:Acute Pain / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000758:Anesthesia; D001943:Breast Neoplasms / Q000235:genetics* / Q000601:surgery*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003080:Cold Temperature; D030541:Databases, Genetic; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006358:Hot Temperature; D006801:Humans; D008875:Middle Aged; D010098:Oxycodone / Q000627:therapeutic use; D010147:Pain Measurement; D010149:Postoperative Pain / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000701:Analgesics, Opioid; D010098:Oxycodone; D002394:Catechol O-Methyltransferase