Apraclonidine attenuates the increases in spinal excitatory amino acid release in rats with adjuvant-induced inflammation.

Abstract

The release of excitatory amino acids (EAAs), nitric oxide, and prostaglandins plays a critical role in the development of peripheral tactile and thermal hypersensitivity after the induction of knee joint inflammation. In this study, we used a model of chronic spinal microdialysis to examine the effect of complete Freund's adjuvant (CFA)-induced inflammation on the spinal release of EAAs and also assessed the antinociceptive effect of a new alpha(2)-adrenergic agonist, apraclonidine, by using this model. Male Sprague-Dawley rats were implanted with microdialysis catheters. CFA was injected into the plantar surface of the left hindpaw to induce inflammation. Concentrations of amino acids in dialysate and thermal and tactile withdrawal latency were evaluated for 1 wk. Intraplantar injection of CFA evoked a significant release of glutamate, aspartate, and citrulline for 6 days. Three milligrams of intraperitoneal apraclonidine significantly suppressed the release of EAAs and citrulline. Apraclonidine was given intraperitoneally 2--3 days after CFA injection. Prominent thermal and tactile allodynia was observed for 6 days. Our results show that the significant modulatory effect of the alpha(2)-adrenergic agonist apraclonidine on the release of EAAs may account for its antinociceptive properties in adjuvant-induced inflammation. This study showed a novel finding that the hypersensitivity state seems to be dependent on increased release of spinal excitatory amino acids (EAAs), and the significant modulatory effect of the alpha(2)-adrenergic agonist apraclonidine on the release of spinal EAAs accounts for its analgesic properties in adjuvant-induced inflammation.