title: Role of 5-HT5A and 5-HT1B/1D receptors in the antinociception produced by ergotamine and valerenic acid in the rat formalin test.
abstract: Sumatriptan, dihydroergotamine and methysergide inhibit 1% formalin-induced nociception by activation of peripheral 5-HT1B/1D receptors. This study set out to investigate the pharmacological profile of the antinociception produced by intrathecal and intraplantar administration of ergotamine (a 5-HT1B/1D and 5-HT5A/5B receptor agonist) and valerenic acid (a partial agonist at 5-HT5A receptors). Intraplantar injection of 1% formalin in the right hind paw resulted in spontaneous flinching behavior of the injected hindpaw of female Wistar rats. Intrathecal ergotamine (15nmol) or valerenic acid (1 nmol) blocked in a dose dependent manner formalin-induced nociception. The antinociception by intrathecal ergotamine (15nmol) or valerenic acid (1nmol) was partly or completely blocked by intrathecal administration of the antagonists: (i) methiothepin (non-selective 5-HT5A/5B; 0.01-0.1nmol); (ii) SB-699551 (selective 5-HT5A; up to 10nmol); (iii) anti-5-HT5A antibody; (iv) SB-224289 (selective 5-HT1B; 0.1-1nmol); or (v) BRL-15572 (selective 5-HT1D; 0.1-1nmol). Likewise, antinociception by intraplantar ergotamine (15nmol) and valerenic acid (10nmol) was: (i) partially blocked by methiothepin (1nmol), SB-699551 (10nmol) or SB-224289 (1nmol); and (ii) abolished by BRL-15572 (1nmol). The above doses of antagonists (which did not affect per se the formalin-induced nociception) were high enough to completely block their respective receptors. Our results suggest that ergotamine and valerenic acid produce antinociception via 5-HT5A and 5-HT1B/1D receptors located at both spinal and peripheral sites. This provides new evidence for understanding the modulation of nociceptive pathways in inflammatory pain.
authors.affiliation: Laboratories of Neurobiology of Pain and Cardiovascular Pharmacology, Departamento de Farmacobiología, Cinvestav, Sede Sur, México D.F., México.
authors.forename: Guadalupe C
authors.initials: GC
authors.lastname: Vidal-Cantú
authors.affiliation: Universidad La Salle, México D.F., México.
authors.forename: Mildred
authors.initials: M
authors.lastname: Jiménez-Hernández
authors.affiliation: Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, México D.F., México.
authors.forename: Héctor I
authors.initials: HI
authors.lastname: Rocha-González
authors.affiliation: Laboratories of Neurobiology of Pain and Cardiovascular Pharmacology, Departamento de Farmacobiología, Cinvestav, Sede Sur, México D.F., México.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
authors.affiliation: Laboratories of Neurobiology of Pain and Cardiovascular Pharmacology, Departamento de Farmacobiología, Cinvestav, Sede Sur, México D.F., México.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
authors.affiliation: Departamento de Biología Celular, Instituto Nacional de Perinatología, Secretaría de Salud, Montes Urales 800, Col. Lomas Virreyes, 11000 México D.F., México; Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas, México. Electronic address: islas_m@yahoo.com.mx.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Muñoz-Islas
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004878:Ergotamine / Q000494:pharmacology*; D005260:Female; D005557:Formaldehyde / Q000009:adverse effects*; D007192:Indenes / Q000494:pharmacology*; D059225:Nociception / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D007192:Indenes; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D012702:Serotonin Antagonists; D012717:Sesquiterpenes; D044282:Receptor, Serotonin, 5-HT1A; D005557:Formaldehyde; C037133:valerenic acid; D004878:Ergotamine
keywords: 5-HT(1B/1D) receptors; 5-HT(5A) receptors; 5-hydroxytriptamine (PubChem CID: 5202); BRL-15572 didydrochloride (PubChem CID: 9891303); Dimethyl sulphoxide (PubChem CID: 679); Ergotamine; Inflammatory pain; SB-224289 hydrochloride (PubChem CID: 3378093); SB-699551; Valerenic acid