PURPOSE: The purpose of this study was to determine the mechanisms of nitrous oxide (N2O) antinociception at the spinal level with yohimbine (an α2-adrenergic antagonist) and flumazenil (a specific benzodiazepine antagonist) using chemonociceptive stimuli in spinal dorsal horn neurons in the cat. METHODS: A lumbar laminectomy extending from L4 to L6 was performed to allow insertion of a extracellular recording device via a microelectrode. Additional laminectomy was performed at the T12 level to transect the spinal cord. As a noxious stimulus, bradykinin (BK) was injected via the cannula inserted into the femoral artery. Animals were divided into four treatment groups for subsequent experiments: N2O+flumazenil, N2O+yohimbine, flumazenil (alone), and yohimbine (alone). RESULTS: N2O suppressed BK-induced nociceptive responses in transected feline spinal cords. The BK-induced neuronal firing rates were significantly suppressed: to 69.2%, 61.8%, and 52.2% of the baseline firing rate at 10, 20, and 30 min, respectively, after N2O administration. The 47.8% suppression on BK-induced neuronal responses at 30 min after N2O administration was reversed 5 min after administration of yohimbine (25.2% suppression). Similarly, N2O suppression (42.5%) on chemically induced neuronal responses was reversed by flumazenil (24.9% suppression) at identical postadministration intervals. CONCLUSION: These data imply that N2O suppresses the nociceptive responses in part probably through its agonistic binding activity to the α2-adrenergic, γ-aminobutyric acid (GABA)-benzodiazepine, or both receptor systems in dorsal born neurons of the feline spinal cord.
PURPOSE: The purpose of this study was to determine the mechanisms of nitrous oxide (N2O) antinociception at the spinal level with yohimbine (an α2-adrenergic antagonist) and flumazenil (a specific benzodiazepine antagonist) using chemonociceptive stimuli in spinal dorsal horn neurons in the cat. METHODS: A lumbar laminectomy extending from L4 to L6 was performed to allow insertion of a extracellular recording device via a microelectrode. Additional laminectomy was performed at the T12 level to transect the spinal cord. As a noxious stimulus, bradykinin (BK) was injected via the cannula inserted into the femoral artery. Animals were divided into four treatment groups for subsequent experiments: N2O+flumazenil, N2O+yohimbine, flumazenil (alone), and yohimbine (alone). RESULTS:N2O suppressed BK-induced nociceptive responses in transected feline spinal cords. The BK-induced neuronal firing rates were significantly suppressed: to 69.2%, 61.8%, and 52.2% of the baseline firing rate at 10, 20, and 30 min, respectively, after N2O administration. The 47.8% suppression on BK-induced neuronal responses at 30 min after N2O administration was reversed 5 min after administration of yohimbine (25.2% suppression). Similarly, N2O suppression (42.5%) on chemically induced neuronal responses was reversed by flumazenil (24.9% suppression) at identical postadministration intervals. CONCLUSION: These data imply that N2O suppresses the nociceptive responses in part probably through its agonistic binding activity to the α2-adrenergic, γ-aminobutyric acid (GABA)-benzodiazepine, or both receptor systems in dorsal born neurons of the feline spinal cord.