Deletion of mu-opioid receptor in mice does not affect the minimum alveolar concentration of volatile anaesthetics and nitrous oxide-induced analgesia.
BACKGROUND
The role of the endogenous opioid system in the anaesthetic effect of volatile anaesthetics and the analgesic action of nitrous oxide (N2O) is unclear. In the current study, we investigated whether the mu-opioid receptor (MOP) is involved in these activities using MOP knockout (MOP-KO) and wild-type (WT) mice.


METHODS
Minimum alveolar concentrations (MACs) for sevoflurane, isoflurane, and halothane, and the sevoflurane MAC-sparing effect of N2O were determined in homozygous MOP-KO and WT mice. The analgesic effect of N2O and the suppressive effect of naloxone on N2O analgesia were assessed in a writhing test and a hot-plate test. Immunohistochemical staining was used to visualize N2O-induced c-Fos expression in the lumbar spinal cord.


RESULTS
There were no significant differences in the MAC values of the three volatile anaesthetics or in the sevoflurane MAC-sparing effect of N2O 70% between MOP-KO and WT mice. There was also no significant difference in the analgesic effect of N2O 70% or in the level of c-Fos expression induced by N2O 70% between the two genotypes. In the writhing test, naloxone significantly attenuated N2O analgesia in MOP-KO and WT mice.


CONCLUSIONS
These results suggest that MOP is not required for the anaesthetic action of volatile anaesthetics and the analgesic effect of N2O. Opioid receptors other than MOP may mediate the analgesic action of N2O.
Koyama
T
T
Department of Anaesthesia, Kyoto University Hospital, Kyoto, Japan.
Mayahara
T
T
Wakamatsu
T
T
Sora
I
I
Fukuda
K
K
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004347:Drug Interactions; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009609:Nitrous Oxide / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D011930:Reaction Time / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D017450:Receptors, Opioid, mu; D009020:Morphine; D009609:Nitrous Oxide