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 gamma-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-media red 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. (C) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.