Nitrous oxide and the inhibitory synaptic transmission in rat dorsal horn neurons

The analgesic effect of nitrous oxide (N₂O) is thought to depend on noradrenaline release in the spinal cord following activation of descending inhibitory neurons. In addition to this indirect facilitation of inhibition in the spinal cord, we previously showed direct inhibition of glutamate receptors in dorsal horn neurons by N₂O. Since general anesthetics could possibly affect excitatory and/or inhibitory components of synaptic transmission, we sought to evaluate the direct effect of N₂O on inhibitory transmission in spinal cord neurons.

Using whole-cell patch-clamp recording from rat transversal spinal cord slices, we investigated the actions of 50% N₂O and 0.5% isoflurane (both 0.3 rat MAC; minimum alveolar concentration) on exogenously applied γ-aminobutyric acid (GABA)- and glycine-induced currents in rat dorsal horn lamina II neurons. The amplitudes and integrated areas of GABA- and glycine-induced currents were not significantly affected by N₂O, but were increased in the presence of isoflurane. N₂O did not affect the amplitude, frequency or decay time probability distribution of either GABA or glycine receptor-mediated miniature postsynaptic currents. We further sought to determine the effect of N₂O on focal stimulation-evoked synaptic currents mediated by GABA and glycine receptors, and found no effect in the majority of neurons.

These and other findings suggest that N₂O has a discrete action in the spinal cord, distinct from the effects of the volatile anesthetics, consisting of inhibition of excitation in SG neurons through an action on ionotropic glutamatergic receptors and potentiation of inhibition through the descending noradrenergic system.