5-HT2A RECEPTOR SUBTYPE IS INVOLVED IN THE THERMAL HYPERALGESIC MECHANISM OF SEROTONIN IN THE PERIPHERY

The present study was designed to investigate which subtypes of 5-HT r eceptors are involved in 5-HT-induced hyperalgesia using behavioral as sessment of hyperalgesia. 5-HT and various putative agonists for 5-HT receptor subtypes (5-HT1A, 2. 3) were intradermally injected into the rat ipsilateral hindpaw. Paw-withdrawal latency to radiant heat stimul ation was examined every 15 min for 2 h. Injection of 5-HT (30 mu g) a nd 5-HT2A receptor agonist (a-methyl 5-HT; 0.86 mg/kg) significantly r educed the paw-withdrawal latency. On the other hand, injection of 5-H T3 receptor agonists (2-methyl 5-HT; 0.86 mg/kg, m-CPG; 8 mg/kg) did n ot produce hyperalgesia. Furthermore, pretreatment with 5-HT2A recepto r antagonist (ketanserin), but not with 5-HT3 receptor antagonist (tro pisetron), attenuated the behavioral response after the injection of 5 -HT. These findings strongly suggest that the 5-HT2A receptor subtype, but not the 5-HT3 subtype, is involved in 5-HT-induced hyperalgesia i n acute injury and inflammation in the rat. In situ hybridization hist ochemistry revealed the presence of 5-HT2 receptor mRNA in a subpopula tion of both large and small neurons in the rat dorsal root ganglia. ( C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V.