Role of peripheral and spinal 5-HT6 receptors according to the rat formalin test.
The present study assessed the possible pronociceptive role of peripheral and spinal 5-HT(6) receptors in the formalin test. For this, local peripheral administration of selective 5-HT(6) receptor antagonists N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)-benzenesulphonamide (SB-399885) (0.01-1 nmol/paw) and 4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzene-sulfonamide 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(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(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(6) receptors play a pronociceptive role in peripheral as well as spinal sites in the rat formalin test. Thus, 5-HT(6) receptors could be a target to develop analgesic drugs.
Castañeda-Corral
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G
Departamento de Farmacobiología, Cinvestav, Sede Sur, Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330 México, DF, Mexico.
Rocha-González
H I
HI
Araiza-Saldaña
C I
CI
Ambriz-Tututi
M
M
Vidal-Cantú
G C
GC
Granados-Soto
V
V
D000818:Animals; D005260:Female; D005557:Formaldehyde; D006614:Hindlimb; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007267:Injections; D009411:Nerve Endings / Q000378:metabolism; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D017933:Peripheral Nervous System / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor; D005557:Formaldehyde