ROLE OF NMDA AND AMPA GLUTAMATERGIC TRANSMISSION IN SPINAL C-FOS EXPRESSION AFTER URINARY-TRACT IRRITATION

Chemical irritation of the lower urinary tract (LUT) of the rat increa ses the expression of the immediate early gene c-fos within neurons in the dorsal horn (DH), dorsal commissure (DCM), and intermediolateral region, including sacral parasympathetic nucleus (SPN) of the spinal c ord (L(6)-S-1). A previous study indicated the involvement of the N-me thyl-D-aspartic acid (NMDA) receptor in this c-fos expression after LU T irritation. The role of glutamatergic synapses was further investiga ted using a selective and competitive lpha-amino-3-hydroxy-5-methyliso xazole-4-propionic acid (AMPA) receptor antagonist (LY-215490). System ic administration of LY-215490 produced a dose-dependent decrease in t he number of Fos-positive cells after LUT irritation in the DCM and SP N areas, whereas in the DH only the highest dose (10 mg/kg) of LY-2154 90 decreased the number of Fos-positive cells. A low dose (1 mg/kg) of either MK-801 (an NMDA antagonist) or LY-215490 alone did not alter c -fos expression. However, a combined administration of low doses of MK -801 and LY-215490 significantly decreased the number of Fos-positive cells in all regions of the spinal cord. These results indicate that A MPA as well as NMDA receptors are involved in the spinal processing of nociceptive input from the LUT and that these glutamatergic receptors play a synergistic role in visceral nociceptive processing.