Antiallodynic effects of intrathecally administered 5-HT(2C) receptor agonists in rats with nerve injury.
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.
Obata
Hideaki
H
Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Maebashi, Gunma 371-5811, Japan. hobata@showa.gunma-u.ac.jp
Saito
Shigeru
S
Sakurazawa
Shinobu
S
Sasaki
Masayuki
M
Usui
Tadashi
T
Goto
Fumio
F
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D007650:Ketanserin / Q000494:pharmacology; D008026:Ligation; D008159:Lumbar Vertebrae; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D009619:Nociceptors / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013127:Spinal Nerves / Q000293:injuries; D013141:Spiro Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D000662:Amphetamines; D007211:Indoles; D010879:Piperazines; D011719:Pyrazines; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D013449:Sulfonamides; D013876:Thiophenes; C042390:alpha-methylserotonin; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine