title: κ-Opioid receptor mediates the antinociceptive effect of nitrous oxide in mice.
abstract: BACKGROUND
  Our previous reports demonstrated that genetic deletion of μ-opioid receptor has no influence on the anaesthetic and antinociceptive effects of nitrous oxide (N2O) in mice, and that an antagonist selective for κ-opioid receptor (KOP), but not that selective for δ-opioid receptor, suppresses the antinociceptive effect of N2O. However, it is not known whether genetic deletion of KOP affects the N2O actions.
  
  
  METHODS
  We measured the minimum alveolar concentration (MAC) of volatile anaesthetics in the absence and presence of N2O. The antinociceptive action of N2O was tested by an acetic acid-writhing test and a hot-plate test. The number of c-Fos-immunopositive cells in sections from the lumbar spinal cord was counted to test whether the descending inhibitory system participates in the pharmacological action of N2O. The hypnotic action of N2O was assessed by measuring the N2O-induced decrease in the EC50 for loss of the righting reflex (EC50-LORR) of sevoflurane.
  
  
  RESULTS
  Sevoflurane MAC was not significantly reduced by N2O and its antinociceptive action was almost completely abolished in KOP-knockout (KO) mice. The N2O-induced increase in c-Fos-immunopositive cells in laminae III-IV of the lumbar spinal cord was significant in wild-type (WT), but not in KOP-KO mice. In contrast, sevoflurane EC50-LORR was similarly reduced by N2O in WT and KOP-KO mice.
  
  
  CONCLUSIONS
  Our study suggests that N2O demonstrates its antinociceptive action and reduces sevoflurane MAC in mice through KOP activation, whereas its hypnotic potency is not dependent on KOP activation.
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fukagawa
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan kfukuda@kuhp.kyoto-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D007530:Isoflurane / Q000494:pharmacology; D008159:Lumbar Vertebrae; D008738:Methyl Ethers / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009609:Nitrous Oxide / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000172:deficiency / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D000077149:Sevoflurane; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D016760:Proto-Oncogene Proteins c-fos; D017473:Receptors, Opioid, kappa; D000077149:Sevoflurane; D007530:Isoflurane; D009609:Nitrous Oxide
keywords: anaesthetics gases, nitrous oxide; anaesthetics volatile; mice, knockout; potency, analgesic; receptors, opioid, kappa