Allodynia evoked by intrathecal administration of prostaglandin E2 to conscious mice

Abstract

We recently reported that intrathecal (i.t) administration of prostaglandin (PG) F2 alpha to conscious mice induced allodynia that was elicited by non-noxious brushing of the flanks. In the presents study, we demonstrate that i.t. administration of PGD2 and PGE2 to conscious mice also results in allodynia. Dose dependency of PGD2 for allodynia showed a skewed bell-shaped pattern (0.1 ng-2.5 micrograms/mouse), and the maximal allodynic effect was observed with 1.0 microgram at 15 min after intrathecal injection. PGD2-induced allodynia showed a time course and dose dependency similar to that induced by PGF2 alpha, but with lower scores. On the other hand, dose dependency of PGE2 for allodynia showed a bell-shaped pattern over a wide range of dosage from 10 fg to 2.0 micrograms/mouse. The maximal allodynic effect was observed with 0.01-0.1 microgram at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. Intrathecally administered strychnine and the GABAA antagonist bicuculline also induced allodynia in conscious mice. The time courses of allodynia evoked by strychnine and bicuculline coincided with those by PGE2 and PGF2 alpha, respectively. PGE2-induced allodynia was dose-dependently relieved by the strychnine-sensitive glycine receptor agonist taurine, the NMDA receptor antagonist ketamine, and a high dose of the alpha 2-adrenergic agonist clonidine, but not by the GABAA agonist muscimol or by the GABAB agonist baclofen. In contrast, PGF2-induced allodynia was dramatically inhibited by clonidine and baclofen, but not by taurine, ketamine or muscimol.(ABSTRACT TRUNCATED AT 250 WORDS)