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 increases 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 cord (L6-S1). A previous study indicated the involvement of the N-methyl-D-aspartic acid (NMDA) receptor in this c-fos expression after LUT irritation. The role of glutamatergic synapses was further investigated using a selective and competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist (LY-215490). Systemic administration of LY-215490 produced a dose-dependent decrease in the number of Fos-positive cells after LUT irritation in the DCM and SPN areas, whereas in the DH only the highest dose (10 mg/kg) of LY-215490 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 AMPA 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.