Role of peripheral and spinal 5-HT sub(6) receptors according to the rat formalin test

The present study assessed the possible pronociceptive role of peripheral and spinal 5-HT sub(6) receptors in the formalin test. For this, local peripheral administration of selective 5-HT sub(6) receptor antagonists N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)-b e nzenesulphonam...

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Published in:Neuroscience 2009-08, Vol.162 (2), p.444-452
Main Authors: Castaneda-Corral, G, Rocha-Gonzalez, H I, Araiza-Saldana, C I, Ambriz-Tututi, M, Vidal-Cantu, G C, Granados-Soto, V
Format: Article
Language:English
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Summary:The present study assessed the possible pronociceptive role of peripheral and spinal 5-HT sub(6) receptors in the formalin test. For this, local peripheral administration of selective 5-HT sub(6) receptor antagonists N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)-b e nzenesulphonamide (SB-399885) (0.01-1 nmol/paw) and 4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzene-sulfo n amide hydrochloride (SB-258585) (0.001-0.1 nmol/paw) significantly reduced formalin-induced flinching. Local peripheral serotonin (5-HT) (10-100 nmol/paw) or 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole hydrochloride (EMD-386088) (0.01-0.1 nmol/paw; a selective 5-HT sub(6) receptor agonist) augmented 0.5% formalin-induced nociceptive behavior. The local pronociceptive effect of 5-HT (100 nmol/paw) or EMD-386088 (0.1 nmol/paw) was significantly reduced by SB-399885 or SB-258585 (0.1 nmol/paw). In contrast to peripheral administration, intrathecal injection of 5-HT sub(6) receptor antagonists SB-399885 and SB-258585 (0.1-10 nmol/rat) did not modify 1% formalin-induced nociceptive behavior. Spinal 5-HT (50-200 nmol/rat) significantly reduced formalin-induced flinching behavior during phases 1 and 2. Contrariwise, intrathecal EMD-386088 (0.1-10 nmol/rat) dose-dependently increased flinching during phase 2. The spinal pronociceptive effect of EMD-386088 (1 nmol/rat) was reduced by SB-399885 (1 nmol/rat) and SB-258585 (0.1 nmol/rat). Our results suggest that 5-HT sub(6) receptors play a pronociceptive role in peripheral as well as spinal sites in the rat formalin test. Thus, 5-HT sub(6) receptors could be a target to develop analgesic drugs. 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole hydrochloride 4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzene-sulfo n amide hydrochloride N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)-b e nzenesulphonamide
ISSN:0306-4522
DOI:10.1016/j.neuroscience.2009.04.072