ALLODYNIA EVOKED BY INTRATHECAL ADMINISTRATION OF PROSTAGLANDIN E(2) TO CONSCIOUS MICE

We recently reported that intrathecal (i.t.) administration of prostaglandin (PG) F-2 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 PGD(2) and PGE(2) to conscious mice also results in allodynia. Dose dependency of PGD(2) for allodynia showed a skewed bell-shaped pattern (0.1 ng-2.5 mu g/mouse), and the maximal allodynic effect was observed with 1.0 mu g at 15 min after intrathecal injection. PGD(2)-induced allodynia showed a time course and dose dependency similar to that induced by PGF(2 alpha), but with lower scores. On the other hand, dose dependency of PGE(2) for allodynia showed a bell-shaped pattern over a wide range of dosage from 10 fg to 2.0 mu g/mouse. The maximal allodynic effect was observed with 0.01-0.1 mu g at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. Intrathecally administered strychnine and the GABA(A) antagonist bicuculline also induced allodynia in conscious mice. The time courses of allodynia evoked by strychnine and bicuculline coincided with those by PGE(2) and PGF(2 alpha) respectively. PGE(2)-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 GABA(A) agonist muscimol or by the GABA(B) agonist baclofen. In contrast, PGF(2 alpha)-induced allodynia was dramatically inhibited by clonidine and baclofen, but not by taurine, ketamine or muscimol. In addition, PGE(2)-induced hyperalgesia assessed by the hot plate test was not suppressed by taurine or clonidine. These results demonstrate that the mechanism of PGE(2)-induced allodynia is different from that of PGF(2 alpha)-induced allodynia and from that of PGE(2)-induced hyperalgesia.