EFFECTS OF NITRIC-OXIDE AVAILABILITY ON RESPONSES OF SPINAL WIDE DYNAMIC-RANGE NEURONS TO EXCITATORY AMINO-ACIDS

The role of nitric oxide (NO) in responses of spinal dorsal horn neuro ns to excitatory amino acids and to cutaneous mechanical stimuli was e xamined. Extracellular recordings were made from wide dynamic range ne urons excited with ion-tophoretically applied excitatory amino acid ag onists, N-methyl-D-aspartate (NMDA) and lpha-amino-3-hydroxy-5-methyli soxazole-4-propionic acid (AMPA) or kainic acid. Nitric oxide availabi lity was decreased by iontophoretic application of NO synthase inhibit ors, N-omega-nitro-L-arginine methyl ester (L-NAME) or L-N-5-(1-iminoe thyl)ornithine (L-NIO), or elevated by the NO donating compound, S-nit roso-N-penicillamine (SNAP). When cells were excited with successive a pplication of NMDA and non-NMDA excitatory amino acid receptor agonist s, application of NO synthase inhibitors led to a decrease in response s to NMDA in 60% of neurons. In more than a third of the cells tested, inhibition of NO synthase caused reciprocal changes in responses to g lutamate receptor agonists: NMDA-evoked responses were significantly d ecreased whereas responses to the non-NMDA receptor agonists (AMPA or kainic acid) were increased. Application of the NO donating compound, S-nitroso-N-penicillamine, revealed an opposite tendency, increasing r esponses to NMDA in more than half of the neurons tested. In approxima tely 40% of the cells, reciprocal changes in responses to excitatory a mino acid receptor agonists of NMDA versus non-NMDA types were observe d after application of S-nitroso-N-penicillamine, such that the increa se in NMDA responses was accompanied by decreases in the responses to kainic acid. The inhibitory effect of N-omega-nitro-L-arginine methyl ester on the basal firing rate evoked by sustained iontophoretic appli cation of NMDA was specific, dose-dependent and prevented by L-arginin e. In the presence of N-omega-nitro-L-arginine methyl ester, responses to noxious peripheral stimulation were either unchanged or decreased. Responses to innocuous stimuli, however, were significantly elevated by N-omega-nitro-L-arginine methyl ester. These results suggest that a vailability of NO at the synapses between primary afferent fibers and secondary dorsal horn neurons may contribute to the dominancy of one t ype of excitatory amino acid receptor class over the other in transmis sion of somatosensory information.