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

PURPOSE

The purpose of this study was to determine the mechanisms of nitrous oxide (NO) antinociception at the spinal level with yohimbine (an α-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: NO+flumazenil, NO+yohimbine, flumazenil (alone), and yohimbine (alone).

RESULTS

NO 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 NO administration. The 47.8% suppression on BK-induced neuronal responses at 30 min after NO administration was reversed 5 min after administration of yohimbine (25.2% suppression). Similarly, NO suppression (42.5%) on chemically induced neuronal responses was reversed by flumazenil (24.9% suppression) at identical postadministration intervals.

CONCLUSION

These data imply that NO suppresses the nociceptive responses in part probably through its agonistic binding activity to the α-adrenergic, γ-aminobutyric acid (GABA)-benzodiazepine, or both receptor systems in dorsal born neurons of the feline spinal cord.