ANTAGONISM OF NITROUS-OXIDE ANTINOCICEPTION IN THE RAT HOT PLATE TESTBY SITE-SPECIFIC MU-OPIOID AND EPSILON-OPIOID RECEPTOR BLOCKADE

The analgesic property of the anesthetic gas N2O has long been known a nd used to treat pain in clinical medicine and dentistry. The present study was conducted to identify by subtype and possible location the b rain opioid receptors that mediate N2O antinociception in rats. A 5-mi n exposure to 70% N2O consistently evoked an antinociceptive effect in the hot plate test. This drug effect was partly antagonized in dose-r elated fashion by i.c.v. pretreatment with naltrexone, D-Phe-Cys-Tyr-D -Trp-Orn-Thr-Pen-Thr-NH2 and beta-endorophin(1-27), which block multip le, mu and epsilon opioid receptors, respectively. However, the N2O-ev oked antinociception was unaffected by i.c.v. pretreatment with either the delta opioid antagonist naltrindole or the kappa opioid antagonis t nor-binaltorphimine. When D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 wa s administered intracerebrally directly into the periaqueductal gray, N2O antinociception was partly antagonized in a dose-dependent manner. The antinociceptive response to N2O was uninfluenced by beta-endorphi n(1-27) administered into the periaqueductal gray. The findings of the se pharmacological antagonism studies are consistent with the hypothes is that exposure to N2O causes a neuronal release of P-endorphin. Thes e results indicate that supraspinal mu and epsilon opioid receptors me diate N2O antinociception in the rat hot plate paradigm and that one c entral site of such mu but not epsilon opioid receptors is the periaqu eductal gray.