title: Role of spinal 5-HT5A, and 5-HT1A/1B/1D, receptors in neuropathic pain induced by spinal nerve ligation in rats.
abstract: Serotonin (5-HT) participates in pain modulation by interacting with different 5-HT receptors. The role of 5-HT5A receptor in neuropathic pain has not previously studied. The purpose of this study was to investigate: A) the role of 5-HT5A receptors in rats subjected to spinal nerve injury; B) the expression of 5-HT5A receptors in dorsal spinal cord and dorsal root ganglia (DRG). Neuropathic pain was induced by L5/L6 spinal nerve ligation. Tactile allodynia in neuropathic rats was assessed with von Frey filaments. Western blot methodology was used to determine 5-HT5A receptor protein expression. Intrathecal administration (on day 14th) of 5-HT (10-100 nmol) or 5-carboxamidotryptamine (5-CT, 0.03-0.3 nmol) reversed nerve injury-induced tactile allodynia. Intrathecal non-selective (methiothepin, 0.1-0.8 nmol) and selective (SB-699551, 1-10 nmol) 5-HT5A receptor antagonists reduced, by ~60% and ~25%, respectively, the antiallodynic effect of 5-HT (100 nmol) or 5-CT (0.3 nmol). Moreover, both selective 5-HT1A and 5-HT1B/1D receptor antagonists, WAY-100635 (0.3-1 nmol) and GR-127935 (0.3-1 nmol), respectively, partially diminished the antiallodynic effect of 5-HT or 5-CT by about 30%. Injection of antagonists, by themselves, did not affect allodynia. 5-HT5A receptors were expressed in the ipsilateral dorsal lumbar spinal cord and DRG and L5/L6 spinal nerve ligation did not modify 5-HT5A receptor protein expression in those sites. Results suggest that 5-HT5A receptors reduce pain processing in the spinal cord and that 5-HT and 5-CT reduce neuropathic pain through activation of 5-HT5A and 5-HT1A/1B/1D receptors. These receptors could be an important part of the descending pain inhibitory system.
authors.affiliation: Neurobiology of Pain Laboratory, 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.forename: Sabino Hazael
authors.initials: SH
authors.lastname: Avila-Rojas
authors.affiliation: Neurobiology of Pain Laboratory, 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.forename: Isabel
authors.initials: I
authors.lastname: Velázquez-Lagunas
authors.affiliation: Neurobiology of Pain Laboratory, 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.forename: Ana Belen
authors.initials: AB
authors.lastname: Salinas-Abarca
authors.affiliation: Neurobiology of Pain Laboratory, 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.forename: Paulino
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.affiliation: Neurobiology of Pain Laboratory, 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.forename: Jorge Baruch
authors.initials: JB
authors.lastname: Pineda-Farias
authors.affiliation: Neurobiology of Pain Laboratory, 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@prodigy.net.mx.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D008159:Lumbar Vertebrae; D008719:Methiothepin / Q000494:pharmacology; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013127:Spinal Nerves / Q000293:injuries*; D014110:Touch
chemical_list: D000700:Analgesics; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C078730:serotonin 5 receptor; D044282:Receptor, Serotonin, 5-HT1A; C090701:GR 127935; D012701:Serotonin; D008719:Methiothepin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C047087:5-carboxamidotryptamine
keywords: 5-HT(5A) receptors; Neuropathy; Serotonin; Spinal cord; Tactile allodynia