title: The involvement of the nociceptin receptor in the antinociceptive action of nitrous oxide.
abstract: Nociceptin and its receptor are widely expressed in the central nervous system and are involved in the modulation of nociception. We have previously reported that the minimum anesthetic alveolar concentrations for volatile anesthetics do not differ between nociceptin receptor knockout (NOP-/-) mice and wild-type (NOP+/+) mice. In the present study, we investigated whether the nociceptin system is involved in the antinociceptive action of nitrous oxide. Using the acetic acid-induced writhing test, we showed that nitrous oxide had significantly less analgesic action in NOP-/- mice than in NOP+/+ mice. Furthermore, when anesthetized with a mixture of halothane and nitrous oxide (70%), intraperitoneal injection of acetic acid resulted in an increase of plasma adrenocorticotropic hormone concentrations in NOP-/- mice but not in NOP+/+ mice. An immunohistochemical study showed that nitrous oxide exposure induced c-Fos expression in the spinal cords of NOP+/+ mice but not in those of NOP-/- mice. These results together suggest that the antinociceptive action of nitrous oxide is, at least partly, mediated by the nociceptin system.
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan. himukash@kuhp.kyoto-u.ac.jp
authors.forename: Shugaku
authors.initials: S
authors.lastname: Himukashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
authors.forename: Sahoko
authors.initials: S
authors.lastname: Koyanagi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shichino
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D006221:Halothane / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D009609:Nitrous Oxide / Q000378:metabolism / Q000494:pharmacology*; D010147:Pain Measurement; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011957:Receptors, Opioid / Q000737:chemistry* / Q000502:physiology; D013116:Spinal Cord / Q000473:pathology; D000094942:Nociceptin Receptor
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D011957:Receptors, Opioid; D000324:Adrenocorticotropic Hormone; D009609:Nitrous Oxide; D019342:Acetic Acid; D006221:Halothane; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse