N-METHYL-D-ASPARTATE AND NON-N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISMREDUCES FOS-LIKE IMMUNOREACTIVITY IN CENTRAL TRIGEMINAL NEURONS AFTERCORNEAL STIMULATION IN THE RAT

The role of glutamate receptors in processing noxious sensory input fr om the cornea was assessed in barbiturate-anesthetized rats. Animals w ere treated with selective antagonists for N-methyl-D-aspartate or non -N-methyl-D-aspartate receptor subtypes prior to application of mustar d oil to the corneal surface. Neural activation was estimated from the number of neurons that produced Fos, the protein product of the immed iate early gene, c-fos, as detected by immunocytochemistry. Fos-positi ve neurons were found at two distinct regions of the spinal trigeminal nucleus: the subnucleus interpolaris/caudalis transition and the subn ucleus caudalis/upper cervical cord transition. The number of Fos-posi tive neurons was reduced dose-dependently by the competitive N-methyl- D-aspartate receptor antagonist, (+/-)-2-carboxypiperazin-4-yl]-propyl -1-phosphonic acid (0.08-8 nmol, i.c.v.), or by the non-N-methyl-D-asp artate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (2.5-250 nmol, i.c.v.). The greatest reduction in Fos-positive cells was seen a t the subnucleus caudalis/upper cervical cord transition after blockad e of either receptor subtype. Combined blockade of N-methyl-D-aspartat e and non-N-methyl-D-aspartate receptors did not cause a further reduc tion in the number of Fos-positive neurons than was seen after the hig hest dose of either antagonist alone. Peripheral or central administra tion of the nitric oxide synthase inhibitor, N-G-nitro-L-arginine meth yl ester, had no effect on the number of Fos-positive neurons after co rneal stimulation. These results suggest that corneal input to neurons at the subnucleus caudalis/upper cervical cord transition, and to a l esser extent, at the subnucleus interpolaris/subnucleus caudalis trans ition depends on excitatory amino acid transmission. Both N-methyl-D-a spartate and non-N-methyl-D-aspartate glutamate receptor subtypes, but not the formation of nitric oxide, contribute to the processing of ac ute corneal stimuli by central trigeminal neurons. (C) 1996 IBRO. Publ ished by Elsevier Science Ltd.