Pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test.
The possible pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test was assessed. Local administration of 5-HT7 (SB-269970, 2.5-77.1 nmol/paw), but not 5-HT(1A) (WAY-100635, 1-60 nmol/paw), receptor antagonist significantly reduced formalin-induced flinching. Local 5-hydroxytryptamine (5-HT, 3-100 nmol/paw) or 5-carboxamidotryptamine (5-CT, 0.3-3 nmol/paw) (a 5-HT7/1A receptor agonist) augmented, in a dose-dependent manner, 0.5% formalin-induced nociceptive behavior. The local pronociceptive effect of 5-HT or 5-CT was significantly reduced by SB-269970 (25 and 77.1 nmol/paw), but not by WAY-100635 (10 nmol/paw). 5-HT7 receptors were observed in myelinated and unmyelinated axons of the digital nerves in rat hindpaw. Intrathecal SB-269970 (2.5-77.1 nmol/rat) or WAY-100635 (1-50 nmol/rat) did not modify 1% formalin-induced nociceptive behavior. Spinal 5-HT (25-200 nmol/rat) significantly reduced formalin-induced flinching behavior during phase 2. At lower doses (0.1-3 nmol/rat) intrathecal 5-CT dose-dependently increased flinching during phase 2. In contrast, higher doses (10-30 nmol/rat) of 5-CT reduced formalin-induced nociceptive behavior during both phases. The spinal pronociceptive effect of 5-CT was reduced by SB-269970 (7.7-77 nmol/rat), but not by WAY-100635 (10 nmol/rat). In addition, the spinal antinociceptive effect of 5-CT was partially reversed by WAY-100635 (10 nmol/rat). The spinal antinociceptive effect of 5-HT was unaffected either by SB-269970 (77 nmol/rat) or WAY-100635 (10 nmol/rat). Data suggest that 5-HT7, but not 5-HT1A, receptors play a pronociceptive role in peripheral and spinal sites in the rat formalin test.
Rocha-González
Héctor I
HI
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330 México, D.F., Mexico.
Meneses
Alfredo
A
Carlton
Susan M
SM
Granados-Soto
Vinicio
V
D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology*; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000008:administration & dosage; D012702:Serotonin Antagonists / Q000008:administration & dosage; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage*; D013778:Tetrazolium Salts / Q000008:administration & dosage; D013997:Time Factors
D010636:Phenols; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D013778:Tetrazolium Salts; C104425:serotonin 7 receptor; C075453:5-cyano-2,3-ditolyltetrazolium; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide