The contribution of peripheral 5-hydroxytryptamine2A receptor to carrageenan-evoked hyperalgesia, inflammation and spinal Fos protein expression in the rat.

The present study was conducted to test the hypothesis that the peripheral 5-hydroxytryptamine (5-HT)2A receptor is involved in inflammatory hyperalgesia and production of noxious stimulus-induced neuronal activity at the level of the spinal cord dorsal horn. Intraplantar (i.pl.) injection of carrageenan dramatically reduced paw withdrawal latency to noxious heat (47 degrees C) and caused paw swelling. Pretreatment with ketanserin, a selective antagonist of 5-HT2A receptor, in the hindpaw produced dose-dependent inhibition of the hyperalgesia (0.5, 3 and 5 mug; i.pl.) with full relief at 5 mug. The drug also moderately reduced carrageenan-induced paw swelling in a dose-dependent manner. Carrageenan induced conspicuous expression of c-fos-like immunoreactivity (FLI) in the spinal dorsal horn of segments L4-5. Ketanserin (5 mug) markedly reduced carrageenan-induced FLI in all laminae of the dorsal horn. However, blockade of peripheral 5-HT1A receptors by (N-2-[4-(2-methoxyphenyl-1-piperazinyl] ethyl]-N-2-pyridinylcyclohexanecarboxamide at maximally effective doses (30 and 100 mug; i.pl.) did not alter carrageenan-induced hyperalgesia, edema or expression of FLI. The present study provided evidence at cellular level that the peripheral 5-HT2A receptor is preferentially involved in the development of thermal hyperalgesia in the carrageenan model of inflammation.