Yohimbine and flumazenil: effect on nitrous oxide-induced suppression of dorsal horn neurons in cats

Abstract

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.

Keywords: Flumazenil; N2O; Nociceptive response; Spinal dorsal horn neuron; Yohimbine.