| Research Abstract |
We have investigated the concentration of NO metabolites (NO2-+NO3, NO2-/NO3-) and glutamate in the cerebrospinal fluid, and the contents of cGMP in the dorsal horn following the activation of spinal NMDA receptors, concomitantly observing pain-related behavior, in unanesthetized, free-moving rats using an intrathecal microdialysis method. Intrathecal perfusion of NMDA produced pain-related behavior and increased glutamate and NO2-/NO3- concentrations, in a dose-dependent manner. A competitive NMDA receptor antagonist D, L-2-amino-5-phosphonovaleric acid completely blocked the NMDA-induced responses. A NO synthase inhibitor NG monomethyl-L-arginine acetate (L-NMDA) at the dose, of which completely blocked the increase in NO2-/NO3-, inhibited NMDA-induced pain-related behavior and increase in glutamate concentration. In addition, a soluble guanylyl cyclase inhibitor 1H-[1, 2, 4]oxadiazole[4, 3-a]quinoxaline-1-one significantly also inhibited NMDA-induced pain-related behavior and increase in glutamate concentration. The analysis of cGMP showed that NMDA induced an increase in cGMP in the dorsal half of the spinal cord, which was blocked by L-NMMA. The results in this study have indicated that the activation of NMDA receptor modulated pain-related behavior via NO/cGMP/glutamate release cascade within the spinal cord.
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