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

Abstract Intrathecal administration of serotonin type 2 (5-HT 2 ) receptor agonists, α-methyl-5-hydroxytryptamine maleate (α-m-5-HT) or (±)-1-(4-iodo-2,5-dimethoxyphenyl)-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-HT 2C 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-HT 2C receptor agonist, 6-chloro-2-(1-piperazinyl)-pyrazine (MK212; 3–100 μg), 1-( m -chlorophenyl)-piperazine (mCPP; 30–300 μg), or 1-( m -trifluoromethylphenyl)-piperazine (TFMPP; 30–300 μg), produced antiallodynic effects in a dose-dependent manner with no associated motor weakness. The ED 50 values of MK212, mCPP, and TFMPP were 39.2, 119.9, and 191.9 μg, respectively. Intrathecal pretreatment with the selective 5-HT 2C receptor antagonist RS-102221 (30 μg) diminished the effects of the highest doses of 5-HT 2C receptor agonists. The preferential 5-HT 2A receptor antagonist ketanserin (30 μg) did not reverse the effects. In contrast to 5-HT 2C receptor agonists, the antiallodynic effects of intrathecally administered α-m-5-HT (30 μg) and DOI (100 μg) were reversed by ketanserin, but not by RS-102221. These results indicate that 5-HT 2C receptors have a role in spinal inhibition of neuropathic pain, and the effects produced by intrathecal administration of 5-HT 2C receptor agonists are mediated by a mechanism different from that of α-m-5-HT or DOI, which seem to produce their effects through 5-HT 2A receptors.