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)

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The intrathecal administration of prostaglandin F2 alpha to conscious mice resulted in spontaneous agitation and touch-evoked agitation (allodynia) in the animals. The maximum allodynia induced by prostaglandin F2 alpha was observed at 10-15 min after intrathecal injection, and the response did not disappear by 120 min. Prostaglandin F2 alpha produced allodynia over a wide range of dosage from 0.1 pg to 2.5 micrograms/mouse. Dose dependency of prostaglandin F2 alpha for allodynia showed a skewed bell-shaped pattern, and the maximal allodynic effect was observed at 1.0 microgram. This allodynia was dose-dependently relieved by alpha 1-adrenergic (methoxamine), alpha 2-adrenergic (clonidine), and A1-adenosine (RPIA) agonists. Clonidine was 1.5 orders of magnitude more potent than methoxamine in blocking prostaglandin F2 alpha-induced allodynia. The blockade by clonidine was dose-dependently reversed by the alpha 2-adrenergic antagonist yohimbine but not by the alpha 1-adrenergic antagonist prazosin. These results demonstrate that prostaglandin F2 alpha administered intrathecally induces allodynia in conscious mice and that the allodynia involves the alpha 2-adrenergic and A1-adenosine systems. Because this allodynia has a clear resemblance to the characteristics of chronic pain in patients with causalgia and reflex sympathetic dystrophy, prostaglandin F2 alpha may be involved in allodynia observed with these disorders.

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