NITRIC-OXIDE MEDIATES ALLODYNIA INDUCED BY INTRATHECAL ADMINISTRATION OF PROSTAGLANDIN E(2) OR PROSTAGLANDIN-F2-ALPHA IN CONSCIOUS MICE

We recently reported that intrathecal (i.t.) administration of prostaglandin (PG) E(2) or PGF(2 alpha) in conscious mice induced allodynia through a pathway that includes the glutamate receptor system. Allodynia induced by PGE(2) and PGF(2 alpha) was blocked by antagonists for NMDA and metabotropic glutamate receptor subtypes, respectively, In the present study, we examined the possibility for the involvement of nitric oxide (NO) in the PG-evoked alodynia. Allodynia was assessed once every 5 min by light stroking of the flank of mice with a paintbrush. Intrathecal administration of L-arginine, a substrate of nitric oxide synthase (NOS), in conscious mice resulted in allodynia. Dose dependency of L-arginine for allodynia showed a bell-shaped pattern (1-10 mu g/mouse). The maximal allodynic effect was observed with 5.0 mu g at 10-15 min after i.t. injection, similar in time course and magnitude to that induced by L-glutamate. L-Arginine-induced allodynia was dose-dependently reduced by the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) and the soluble guanylate cyclase inhibitor methylene blue with IC50 values of 7.68 and 8.70 pg/mouse, respectively. PGE(2)-induced allodynia was also dose-dependently inhibited by L-NAME and methylene blue with IC50 values of 94.7 and 74.9 pg/mouse. PGF(2 alpha)-induced allodynia was inhibited by methylene blue with an IC50 value of 40.6 pg/mouse, but not by L-NAME at doses up to 1.0 ng. These results demonstrate that PGE(2)-induced allodynia is mediated through the NO-generating system and that PGF(2 alpha)-induced allodynia may be mediated by interactions with the NO system at a site different from the NO-generating site in the spinal cord.