| This study investigated the cellular signaling pathway involved in 5-HT2A receptor-mediated thermal hyperalgesia in the periphery. It also explored the cellular mechanism of 5-HT-induced hyperalgesia. In addition, the effects of topical application of ketanserin paste on thermal hyperalgesia produced by intraplantar carrageenan and on mechanical allodynia induced by incision in the paw were also determined. The results are listed in the following.1. α -M-5-HT, a selective 5-HT2A agonist, intraplanterly administered into hindpaw, dose-dependently (2μg, 10μg, 50μg) induced thermal hyperalgesia to 47℃ water bath. Chelerythrine, a selective protein kinase C inhibitor, given 10 min before α-M-5-HT , dose-dependently ( 2μg, 6μg, 10μg ) suppressed the thermal hyperalgesia induced by α -M-5-HT (50μg);2. I.pl 5-HT at a dose of 50μg also induced thermal hyperalgesia and this response was suppressed completely by pretreatment with chelerythrine (10 μg, i.pl).3. 8-OH-DPAT, a selective 5-HT1A receptor agonist, at a dose of 100μg induced thermal hyperalgesia moderately. However, pretreatment with i.pl chelerythrine had no effect on the 8-OH-DPAT-induced response.4. 5-HT and α -M-5-HT injected into the hindpaw at a dose of 50μg, both produced a great increase in the expression of c-fos protein in the dorsal horn of rat spinal cord (L5-L6) which were located predominately in laminae I-II. Chelerythrine at a dose of 10μg significantly decreased 5-HT- and α -M-5-HT-induced the expressions of c-fos; 8-OH-DPAT given intraplantarly at a dose of 100μg didn't result in any change of c-fos expression;5. Intraplantar injection of 1% carrageenan (100μl) induced thermalhyperalgesia which peaked at 5 hours. Mechanical allodynia induced by incision that was done in the hindpaw (1.5 cm) lasted 15 days. Ketanserin topically applied remarkably alleviated carrageenan-induced thermal hyperalgesia and incision-induced mechanical allodynia.
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