Antiallodynic effect of intrathecally administered 5-HT2 agonists in rats with nerve ligation

We examined the antiallodynic effect of intrathecally administered serotonin receptor agonists including 5-HT1A, 5-HT1B, 5-HT2 and 5-HT3 receptor subtypes in a rat model using spinal nerve ligation at L5 and L6. Administration of the 5-HT2 receptor agonist, alpha -methyl-5-hydroxytryptamine maleate (alpha -m-5-HT; 3-100 mug) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI; 10-100 mug), 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-HT2 agonists on tactile allodynia were reversed by intrathecal pretreatment with the selective 5-HT2 antagonist ketanserin and with the mixed 5-HT1 and 5-HT2 antagonist methysergide. Neither the mixed 5-HT1A and 5-HT1B antagonist cyanopindolol nor the selective 5-HT3 antagonist MDL72222 attenuated antiallodynic effects induced by 5-HT2 agonists. In contrast, the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT; 1-50 mug), the 5-HT1B agonist 5-methoxy-3-(1,2,5,6-tetrahydro-4-pyridinil)-1H-indol (RU-24969; 10-100 mug) and the 5-HT3 agonist 2-methyl-5-hydroxytryptamine maleate (2-m-5-HT; 30-300 mug) all lacked significant antiallodynic action with intrathecal administration. These results indicate that the 5-HT2 receptor plays an essential role in spinal suppression of neuropathic pain by 5-HT. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.