Antiallodynic effects of intrathecally administered 5-HT2C receptor agonists in rats with nerve injury

Intrathecal administration of serotonin type 2 (5-HT2) receptor agonists, alpha-methyl-5-hydroxytryptamine maleate (alpha-m-5-HT) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyt)-2-aminopropane hydrochloride (DOI), produces antiallodynic effects in a rat model of neuropathic pain. In the present study, we examined the antiallodynic effects of intrathecally administered agents which are selective for 5-HT2C receptors. Allodynia was produced by tight ligation of the left L5 and L6 spinal nerves, and was measured by applying von Frey filaments to the left hindpaw. Administration of the 5-HT2C receptor agonist, 6-chloro-2-(1-piperazinyl)-pyrazine (MK212; 3-100 mug), 1-(m-chlorophenyl)-piperazine (mCPP; 30-300 mug), or 1-(in-trifluoromethylphenyl)-piperazine (TFMPP; 30-300 jig), produced antiallodynic effects in a dose-dependent manner with no associated motor weakness. The ED50 values of MK212, mCPP, and TFMPP were 39.2, 119.9, and 191.9 mug, respectively. Intrathecal pretreatment with the selective 5-HT2C receptor antagonist RS-102221 (30 mug) diminished the effects of the highest doses of 5-HT2C receptor agonists. The preferential 5-HT2A receptor antagonist ketanserin (30 mug) did not reverse the effects. In contrast to 5-HT2C receptor agonists, the antiallodynic effects of intrathecally administered alpha-m-5-HT (30 mug) and DOI (100 mug) were reversed by ketanserin, but not by RS-102221. These results indicate that 5-HT2C receptors have a role in spinal inhibition of neuropathic pain, and the effects produced by intrathecal administration of 5-HT2C receptor agonists are mediated by a mechanism different from that of alpha-m-5-HT or DOI, which seem to produce their effects through 5-HT2A receptors. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.