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Obata H, Saito S, Sakurazawa S, Sasaki M, Usui T, Goto F: Antiallodynic effects of intrathecally administered 5-HT (2C) receptor agonists in rats with nerve injury. Pain. 2004 Mar;108(1-2):163-9.
Intrathecal administration of serotonin type 2 (5-HT (2)) receptor agonists, alpha-methyl-5-hydroxytryptamine maleate (alpha-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 microg), 1-(m-chlorophenyl)-piperazine (mCPP; 30-300 microg), or 1-(m-trifluoromethylphenyl)-piperazine (TFMPP; 30-300 microg), 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 microg, respectively. Intrathecal pretreatment with the selective 5-HT (2C) receptor antagonist RS-102221 (30 microg) diminished the effects of the highest doses of 5-HT (2C) receptor agonists. The preferential 5-HT (2A) receptor antagonist ketanserin (30 microg) did not reverse the effects. In contrast to 5-HT (2C) receptor agonists, the antiallodynic effects of intrathecally administered alpha-m-5-HT (30 microg) and DOI (100 microg) 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 alpha-m-5-HT or DOI, which seem to produce their effects through 5-HT (2A) receptors. |
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