Antiallodynic effect of intrathecally administered 5-HT(2) agonists in rats with nerve ligation.
We examined the antiallodynic effect of intrathecally administered serotonin receptor agonists including 5-HT(1A), 5-HT(1B), 5-HT(2) and 5-HT(3) receptor subtypes in a rat model using spinal nerve ligation at L5 and L6. Administration of the 5-HT(2) receptor agonist, alpha-methyl-5-hydroxytryptamine maleate (alpha-m-5-HT; 3-100 microg) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI; 10-100 microg), showed dose-dependent antiallodynic actions with no associated motor weakness. The antiallodynic action of alpha-m-5-HT was more potent than that of DOI. The effects of 5-HT(2) agonists on tactile allodynia were reversed by intrathecal pretreatment with the selective 5-HT(2) antagonist ketanserin and with the mixed 5-HT(1) and 5-HT(2) antagonist methysergide. Neither the mixed 5-HT(1A) and 5-HT(1B) antagonist cyanopindolol nor the selective 5-HT(3) antagonist MDL72222 attenuated antiallodynic effects induced by 5-HT(2) agonists. In contrast, the selective 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT; 1-50 microg), the 5-HT(1B) agonist 5-methoxy-3-(1,2,5,6-tetrahydro-4-pyridinil)-1H-indol (RU-24969; 10-100 microg) and the 5-HT(3) agonist 2-methyl-5-hydroxytryptamine maleate (2-m-5-HT; 30-300 microg) all lacked significant antiallodynic action with intrathecal administration. These results indicate that the 5-HT(2) receptor plays an essential role in spinal suppression of neuropathic pain by 5-HT.
Obata
H
H
Department of Anesthesiology and Reanimatology, Gunma University, School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Gunma, Japan. hobata@showa.gunma-u.ac.jp
Saito
S
S
Sasaki
M
M
Ishizaki
K
K
Goto
F
F
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013127:Spinal Nerves / Q000293:injuries
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine