Thermal and mechanical antinociceptive action of spinal vs peripherally administered clonidine in the rat inflamed knee joint model

It has been demonstrated recently that in addition to its spinal analgesic actions, the alpha 2 adrenoreceptor agonist clonidine also has peripheral analgesic activity. Few data are available regarding the antinociceptive effects of spinal vs peripherally delivered clonidine in inflammatory pain. Thus we have studied spinal (intrathecal = i.t.) and peripheral (intra-articular = i.a.) administration of clonidine in the rat inflamed knee joint model. Thermal and mechanical antinociception was assessed in rats over 28 h using a modified Hargreaves box and von Frey hairs after induction of tonic persistent inflammatory pain by injection of a kaolin-carrageenan mixture into the right knee joint. Thirty minutes after injection of kaolin-carrageenan, clonidine was administered via an i.t. catheter or by i.a. injection into the right inflamed knee joint or by subcutaneous injection (s.c.) (highest effective intra-articular dose). The specific site of action was assessed using the alpha 2 antagonist yohimbine i.t., i.a. or s.c. Clonidine i.t. resulted in thermal and mechanical antinociception during ongoing inflammation, which was not enhanced by inflammation. In contrast, i.a. delivery of clonidine, which also produced a dose- dependent thermal and mechanical antinociceptive effect, revealed a leftward shift in the antinociceptive activity produced by ongoing inflammation. Yohimbine inhibited the antinociceptive action of clonidine at the site of delivery. We suggest that clonidine produces potent thermal and mechanical antinociception regardless of the route of administration. However, chronic inflammatory processing appears to enhance the antinociceptive efficacy of the peripheral alpha 2 agonist.