The role of neurokinin 1 (NK1) receptor and possible interaction between NK1 and N-methyl-d-aspartic acid (NMDA) glutamatergic receptors were investigated on spinal c- fos expression after lower urinary tract irritation with acetic acid infusion in rats. At both levels of the first (L1) and sixth lumbar (L6) spinal cord, where most of hypogastric nerve and pelvic nerve afferent terminals project, respectively, the selective NK1 receptor antagonist CP-99,994 dose dependently reduced the total number of c- fos protein (Fos)-positive cells. However, CP-100,263, the enantiomer of CP-99,994 with a very low affinity for NK1receptor, did not have any effect on the total number of Fos-positive cells. Coadministration of a low dose (1 mg/kg) of CP-99,994 and NMDA receptor antagonist (MK-801), either of which alone did not affect c- fos expression, significantly inhibited c- fosexpression at both levels of the spinal cord. Regarding regional differences, the number of Fos-positive cells decreased significantly at all regions of the L6 level, but only at the dorsal horn of the L1 level. These results indicate that NK1 receptor is involved in spinal c- fosexpression after lower urinary tract irritation and that NK1 and NMDA receptors have a synergistic interaction in the spinal processing of nociceptive input from the lower urinary tract.
Increased c-fos expression in spinal neurons after irritation of the lower urinary tract in the rat
