Opiate receptors in the periaqueductal gray mediate analgesic effect of nitrous oxide in rats.
The site of action and the pathways which are activated by nitrous oxide (N2O) to produce an analgesic effect are not well defined. Experiments were designed to determine whether N2O produces analgesia by activating opiate receptors or alpha2-adrenoceptors in periaqueductal gray. The analgesic effect of N2O was determined using the tail flick response to noxious radiant heat in lightly anesthetized rats. Different antagonists were bilaterally microinjected into ventrolateral periaqueductal gray to determine whether the analgesic effect produced by N2O was reversed. The increase in the tail flick latencies produced by N2O was reversed by bilateral microinjection into the ventrolateral part of periaqueductal gray with the opiate receptor antagonist naloxone 2.5 microg/0.5 microl, but not with the alpha2-adrenoceptors antagonist yohimbine 1.5 microg/0.5 microl. These results indicate that the N2O analgesic effect is mediated by activation of opiate receptors, but not alpha2-adrenoceptors, in the periaqueductal gray. Combined with the previous experiments that the N2O analgesic effect is reversed by intrathecal injection of an alpha2-adrenoceptor antagonist but not by an opiate receptor antagonist, it seems likely that N2O causes activation of the opiate receptors in the periaqueductal gray, which in turn activate the noradrenergic descending pathways to the spinal cord to produce the analgesic effect.
Fang
F
F
Department of Anesthesia, Stanford University Medical School, CA 94305-5117, USA.
Guo
T Z
TZ
Davies
M F
MF
Maze
M
M
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009609:Nitrous Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D018712:Analgesics, Non-Narcotic; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D015016:Yohimbine; D009270:Naloxone; D009609:Nitrous Oxide