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PAIN MEDICINE

Apraclonidine Attenuates the Increases in Spinal Excitatory Amino Acid Release in Rats with Adjuvant-Induced Inflammation

Chung- Ren Lin, MD^*, Cheng-Haung Wang, MD^*, P.- C. Wu, BA^*, Zhi-Hong Wen, BA^*, Hartmut Buerkle, MD PhD, and Lin-Cheng Yang, MD^*

*Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung Hsien, Taiwan; and Department of Anesthesiology, Westfaelische Wilhelms-Universität Muenster, Germany

Address correspondence and reprint requests to Lin-Cheng Yang, MD, Department of Anesthesiology, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Shung Hsiang, Kaohsiung Hsien, 833, Taiwan. Address e-mail to lcyang1{at}ms13.hinet.net

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 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 ₂-adrenergic agonist apraclonidine on the release of EAAs may account for its antinociceptive properties in adjuvant-induced inflammation.

IMPLICATIONS: 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 ₂-adrenergic agonist apraclonidine on the release of spinal EAAs accounts for its analgesic properties in adjuvant-induced inflammation.