Effects of Intra-articular Injection of Agmatine and Clonidine into the Knee Joint Cavity on the Induction and Maintenance of Arthritic Pain in Rats

Abstract

Background: Previous studies suggest that systemic administration of agmatine, endogenous ligand for imidazoline receptors has anti-hypernociceptive effects in experimental animal. However the peripheral effects of agmatine on inflammatory pain have not yet been elucidated. Here we examined the effects of intra-articular injection of agmatine in the induction and maintenance phase of arthritic pain. In addition, we sought to determine the potential contribution of imidazoline and α2-adrenergic receptors to the antinociceptive effects using clonidine which is mixed α2-adrenoceptor and imidazoline receptor agonist. Methods: To induce arthritis in rats, 2% lambda-carrageenan (50μl, in saline) was injected into the joint of the right hind limb under enflurane anesthesia. Either agmatine (10, 50, 100μg/40μl) or clonidine (10, 50, 100μg/40μl) was injected into the knee joint cavity immediately before or 4 hr after carrageenan injection. Weight load tests were performed to measure pain-re- lated behavior in freely walking rats. Results: The intraarticular injection of agmatine into the knee joint had no effects in the both phase of induction and maintenance of arthritic pain at any dose tested. However, injection of clonidine reversed arthritic pain, when injected 4 h after carrageenan injection. Conclusions: In rats, agmatine has no peripheral effect on inflammatory pain and imidazoline receptors in the periphery may not contribute to the anti-inflammatory pain. (Korean J Anesthesiol 2008; 54: 656~61)