TY - JOUR
T1 - Role of peripheral and spinal 5-HT6 receptors according to the rat formalin test
AU - Castañeda-Corral, G.
AU - Rocha-González, H. I.
AU - Araiza-Saldaña, C. I.
AU - Ambriz-Tututi, M.
AU - Vidal-Cantú, G. C.
AU - Granados-Soto, V.
N1 - Funding Information:
The authors greatly appreciate the bibliographic assistance of B.Sc. Héctor Vázquez. Gabriela Castañeda-Corral, Héctor I. Rocha-González, Claudia I. Araiza-Saldaña and Mónica Ambriz-Tututi are Conacyt fellows. Claudia I. Araiza-Saldaña is the recipient of the “Apoyos Integrales para la Formación de Doctores en Ciencias” fellowship. This work is part of the M.Sc. dissertation of Gabriela Castañeda-Corral. Partially supported by Conacyt (grant 59879 to V.G.-S.).
PY - 2009/8/18
Y1 - 2009/8/18
N2 - The present study assessed the possible pronociceptive role of peripheral and spinal 5-HT6 receptors in the formalin test. For this, local peripheral administration of selective 5-HT6 receptor antagonists N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)-benzene sulphonamide (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-HT6 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-HT6 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-HT6 receptors play a pronociceptive role in peripheral as well as spinal sites in the rat formalin test. Thus, 5-HT6 receptors could be a target to develop analgesic drugs.
AB - The present study assessed the possible pronociceptive role of peripheral and spinal 5-HT6 receptors in the formalin test. For this, local peripheral administration of selective 5-HT6 receptor antagonists N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)-benzene sulphonamide (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-HT6 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-HT6 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-HT6 receptors play a pronociceptive role in peripheral as well as spinal sites in the rat formalin test. Thus, 5-HT6 receptors could be a target to develop analgesic drugs.
KW - 5-HT receptors
KW - SB-258585
KW - SB-399885
KW - hyperalgesia
KW - peripheral sensitization
KW - spinal processing
UR - http://www.scopus.com/inward/record.url?scp=67649502867&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2009.04.072
DO - 10.1016/j.neuroscience.2009.04.072
M3 - Artículo
C2 - 19422883
SN - 0306-4522
VL - 162
SP - 444
EP - 452
JO - Neuroscience
JF - Neuroscience
IS - 2
ER -