Nitric oxide mediates allodynia induced by intrathecal administration of prostaglandin E2 or prostaglandin F2α in conscious mice

Abstract

We recently reported that intrathecal (i.t.) administration of prostaglandin (PG) E₂ or PGF_2α in conscious mice induced allodynia through a pathway that includes the glutamate receptor system. Allodynia induced by PGE₂ and PGF_2α 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 allodynia. 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 μg/mouse). The maximal allodynic effect was observed with 5.0 μg 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^ω-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. PGE₂ induced allodynia was also dose-dependently inhibited by L-NAME and methylene blue with IC₁₅₀. values of 94.7 and 74.9 pg/mouse. PGF_2α-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 PGEZ-induced allodynia is mediated through the NO-generating system and that PGF_2α-induced allodynia may be mediated by interactions with the NO system at a site different from the NO-generating site in the spinal cord.