Topical ketanserin attenuates hyperalgesia and inflammation in arthritis in rats

We investigated effects of topical application of ketanserin, a 5-HT2A receptor antagonist, on hyperalgesia and edema in the arthritic rat, a chronic pain model with inflammation. Unilateral, but not bilateral, arthritis was induced with intra-articular injection of a mixture of kaolin and carrageenan in one side, as indicated by the shortened paw withdrawal latency and an increase in the circumference of the knee joint. Topical application of ketanserin onto skin over the arthritic joint delivered in a mixture of gelatin, glycerol and kaolin produced dose-dependent attenuation of nociceptive and inflammatory effects resulting from intra-articularly injected kaolin/carrageenan. One and 3% ketanserin produced significant or even complete anti-hyperalgesia, as well as a remarkable anti-inflammatory effect (50-70% reduction of edema) while 0.3% ketanserin and placebo failed to produce any effect. Moreover, the effects of ketanserin were maintained for 13 days without decline. In contrast, 3% ketanserin applied to skin of the knee joint on the non-inflamed side for 2 weeks did not alter nociceptive thresholds of the paw and the size of the knee joint in both the inflamed and non-inflamed limbs. These results indicate that 5-HT2A receptors in the periphery play a significant role in the maintenance and/or development of inflammatory pain. The present study suggests that topical ketanserin is a promising direction for potential clinical exploration to relieve established hyperalgesia and inflammation in arthritis without adverse effects and tolerance.