| The present study was conducted with behavioral and immunohistochemical techniques. The study was designed to test the hypothesis that the peripheral 5-HT2A receptor was involved in the inflammation and hyperalgesia induced by carrageenan.Intraplantar (i.pl) pretreatment with ketanserin, a selective antagonist of 5-HT2A receptor, in the hindpaw produced dose-dependent inhibition (0.5, 3 and 5μg) on the hyperalgesia and paw swelling. The drug also reduced 5-HT or a-m-5-HT-induced expression of c-fos-like immunoreactivity in the spinal dorsal horn of segment L 4-5. However, blockade of peripheral 5-HT1A receptors by WAY-100635 failed to show this inhibition. Topical application of ketanserin at different concentration (0.5%, 1%, 3%) dose dependently inhibited hyperalgesia and knee edema produced by kaolin and carrageenan in arthritic rats. The effects were mediated in the periphery but not in the central nervous system, because ketanserin applied on the contralateral side did not have effects on the hyperalgesia and inflammation.The present study provided evidence that peripheral 5-HT plays an important role in the development of hyperalgesia and inflammation in the carrageenan model of inflammation, and that this effect was mediated by 5-HT2A receptor.
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