Peripheral nitric oxide contributes to both formalin- and NMDA-induced activation of nociceptors: An immunocytochemical study in rats.

Nociceptive c-fos expressions in the dorsal horn following intraplantar injection of two kinds of algogenic agents combined with different doses of nitric oxide (NO) synthase inhibitor (N(omega)-nitro-L-arginine methyl ester (L-NAME)) or of NO donor (L-arginine) were used to explore if NO was involved in the activation of peripheral nociceptors. The results showed that: 1) combined injections of L-NAME with formalin into the plantar aspect of one hindpaw of normal rats elicited a dose-dependent suppression of c-fos expression as compared to that induced by formalin alone; 2) combined injections of L-arginine with formalin elicited considerable enhancement of c-fos expression when the dosages of L-arginine were less than 20 micromol, while it elicited marked suppression of c-fos expression when the dosages were in the range from 50 to 100 micromol; and 3) combined injection of L-NAME with NMDA, a selective agonist for NMDA receptors, into the hindpaw could also inhibit the NMDA-induced c-fos expression in the spinal dorsal horn. These results suggest that endogenously generated concentrations of nitric oxide may enhance the initiation of nociceptive inputs of peripheral nociceptors following local injection of formalin or NMDA.