Effects of nitrous oxide on excitatory synaptic transmission in the spinal dorsal horn

The effects of nitrous oxide (N2O) are thought to be mediated by several pharmacological pathways at different levels of the central nervous system. Here, we focus on excitatory glutamatergic transmission in the superficial dorsal horn of the spinal cord with respect to its importance for the nociceptive processing. The effects of 50% N2O on electrically evoked and spontaneous excitatory glutamatergic transmission and on the response to exogenous administration of NMDA and AMPA receptor agonists were examined in lamina II neurons of adult rat spinal cord slices using the whole-cell patch-clamp technique. Peak amplitudes of A delta - and C-fiber evoked monosynaptic NMDA-and AMPA-receptor mediated excitatory post synaptic currents (EPSCs) were decreased in the presence of N2O. N2O reduced the peak amplitude and integrated area of exogenous NMDA- and AMPA-induced currents. Moreover N2O changed the distribution of miniature EPSC amplitude, but not frequency distribution in most neurons. N2O inhibits glutamatergic transmission in the superficial dorsal horn by modulating the NMDA and AMPA receptors. Our findings raise the possibility that the anti nociceptive effect of N2O may be directly mediated at the level of the spinal cord.