title: Spinal 5-HT₅A receptors mediate 5-HT-induced antinociception in several pain models in rats.
abstract: The antinociceptive role of spinal 5-HT5A receptors in rat models of pain along with their expression was evaluated in the spinal cord and dorsal root ganglion (DRG). Nociception was assessed in the formalin, capsaicin, and acetic acid writhing tests. The expression of 5-HT5A receptors was determined by Western blot analysis. Intrathecal treatment with serotonin (5-HT, 10-100 nmol) or 5-carboxamidotryptamine (5-CT, 0.03-0.3 nmol) dose-dependently prevented 1% formalin-induced nociception. Furthermore, 5-HT reduced capsaicin- and acetic acid-induced nociception. 5-HT- or 5-CT-induced antinociception in the formalin test was diminished by the selective 5-HT5A receptor antagonist N-[2-(dimethylamino)ethyl]-N-[[4'-[[(2-phenylethyl)amino] methyl][1,1'-biphenyl]-4-yl]methyl]cyclopentanepropanamide dihydrochloride (SB-699551; 3 and 10 nmol). In addition, 5-HT-induced spinal antinociception in the capsaicin and acetic acid tests was blocked by SB-699551 (10 nmol). Given alone, intrathecal injection of SB-699551 did not affect nociception induced by any irritant. 5-HT5A receptors were expressed in the dorsal spinal cord and DRG, even though formalin injection increased after 24h 5-HT5A receptor expression only in the spinal cord. Data suggest that 5-HT and 5-CT produce antinociception by activation of spinal 5-HT5A receptors in both the spinal cord and DRG. Furthermore, our results suggest that spinal 5-HT5A receptors play an antinociceptive role in several pain models in rats. 5-HT5A receptors may provide a therapeutic target to develop analgesic drugs.
authors: Departamento de Biología Celular, Instituto Nacional de Perinatología, Secretaría de Salud. Montes Urales 800, Col. Lomas Virreyes, 11000 México, D.F., Mexico.
authors: Enriqueta
authors: E
authors: Muñoz-Islas
authors: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
authors: Guadalupe C
authors: GC
authors: Vidal-Cantú
authors: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
authors: Mariana
authors: M
authors: Bravo-Hernández
authors: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
authors: Claudia
authors: C
authors: Cervantes-Durán
authors: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
authors: Geovanna N
authors: GN
authors: Quiñonez-Bastidas
authors: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
authors: Jorge B
authors: JB
authors: Pineda-Farias
authors: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
authors: Paulino
authors: P
authors: Barragán-Iglesias
authors: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico. Electronic address: vgranados@cinvestav.mx.
authors: Vinicio
authors: V
authors: Granados-Soto
mesh_terms: D019342:Acetic Acid; D000818:Animals; D002211:Capsaicin; D005260:Female; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy*; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C078730:serotonin 5 receptor; D012701:Serotonin; C047087:5-carboxamidotryptamine; D019342:Acetic Acid; D002211:Capsaicin
keywords: 5-HT(5A) receptors; Inflammatory pain; Rat; Serotonin; Spinal cord