Involvement of the kappa-opioid receptor in nitrous oxide-induced analgesia in mice.
Nitrous oxide (N(2)O)-induced analgesia is thought to be mediated by endogenous opioids. We previously showed that the mu-opioid receptor is not required for the analgesic action of N(2)O in mice using a gene knockout approach. In this study, we examined the effect of kappa- (KOP)- or delta-opioid receptor (DOP)-selective antagonists on N(2)O-induced analgesia. The analgesic effect of N(2)O was evaluated using a writhing test. Male C57BL/6 mice aged 7-8 weeks were assigned to control, N(2)O, KOP agonist, and DOP agonist groups. According to the group assignment, mice were pretreated with a KOP antagonist, nor-binaltorphimine (nor-BNI), a DOP antagonist, naltrindole hydrochloride (NTI), a KOP agonist U50488, and a DOP agonist SNC80. Mice in the control, KOP agonist, and DOP agonist groups were exposed to 25% oxygen/75% nitrogen for 30 min, and mice in the N(2)O group were exposed to 25% oxygen/75% N(2)O for 30 min. Nor-BNI [10 mg kg(-1), subcutaneously (s.c.)] significantly suppressed the analgesic effect of N(2)O and U50488. In contrast, NTI (10 mg kg(-1) s.c.) did not significantly affect the analgesic action of N(2)O, but almost completely inhibited the analgesic effect of SNC80. These results suggest that KOP plays an important role in the analgesic effect of N(2)O in mice.
Department of Anesthesia, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. yama8899@gmail.com
Tomohiro
T
Koyama
Kazuhiko
K
Fukuda
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000698:Analgesia; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009609:Nitrous Oxide / Q000494:pharmacology*; D010146:Pain / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D016896:Treatment Outcome
D018712:Analgesics, Non-Narcotic; D001549:Benzamides; D009292:Narcotic Antagonists; D010879:Piperazines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C055382:naltrindole; D009609:Nitrous Oxide