title: Evidence for the participation of peripheral α5 subunit-containing GABAA receptors in GABAA agonists-induced nociception in rats.
abstract: The activation of GABAA receptor by γ-amino butyric acid (GABA) in primary afferent fibers produces depolarization. In normal conditions this depolarization causes a reduction in the release of neurotransmitters. Therefore, this depolarization remains inhibitory. However, previous studies have suggested that in inflammatory pain, GABA shifts its signaling from inhibition to excitation by an increased GABA-induced depolarization. The contribution of peripheral α5 subunit-containing GABAA receptors to the inflammatory pain is unknown. The purpose of this study was to investigate the possible pronociceptive role of peripheral α5 subunit-containing GABAA receptors in the formalin test. Formalin (0.5%) injection into the dorsum of the right hind paw produced flinching behavior in rats. Ipsilateral local peripheral pre-treatment (-10min) with exogenous GABA (0.003-0.03µg/paw) or common GABAA receptor agonists muscimol (0.003-0.03µg/paw), diazepam (0.017-0.056µg/paw) or phenobarbital (1-100µg/paw) significantly increased 0.5% formalin-induced nociceptive behavior. The pronociceptive effects of GABA (0.03µg/paw), muscimol (0.03µg/paw), diazepam (0.056µg/paw) and phenobarbital (100µg/paw) were prevented by either the GABAA receptor antagonist bicuculline (0.01-0.1µg/paw) or selective α5 subunit-containing GABAA receptor inverse agonist L-655,708 (0.017-0.17µg/paw). The α5 subunit-containing GABAA receptor protein was expressed in dorsal root ganglion (DRG) and dorsal spinal cord of naïve rats. The formalin injection did not modify α5 subunit-containing GABAA receptor expression. Overall, these results suggest that peripheral α5 subunit-containing GABAA receptors play a pronociceptive role in the rat formalin test.
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: marianabh26@hotmail.com.
authors.forename: Mariana
authors.initials: M
authors.lastname: Bravo-Hernández
authors.affiliation: Centro de Investigación, División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, 86150 Villahermosa, Tabasco, Mexico. Electronic address: lichoferia@hotmail.com.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Feria-Morales
authors.affiliation: Centro de Investigación, División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, 86150 Villahermosa, Tabasco, Mexico; Hospital Regional de Alta Especialidad "Dr. Juan Graham Casasús", 86103 Villahermosa, Tabasco, Mexico. Electronic address: jetorreslopez@hotmail.com.
authors.forename: Jorge Elías
authors.initials: JE
authors.lastname: Torres-López
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: espparmex@hotmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cervantes-Durán
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Zacatenco, México, D.F., Mexico. Electronic address: rdelgado57@gmail.com.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Delgado-Lezama
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: vinicio_granadossoto@hotmail.com.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico. Electronic address: hector.isaac@gmail.com.
authors.forename: Héctor Isaac
authors.initials: HI
authors.lastname: Rocha-González
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects*; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D058785:GABA-A Receptor Agonists; D007093:Imidazoles; C105490:L 655,708; D021122:Protein Subunits; D011963:Receptors, GABA-A; D005557:Formaldehyde; D001640:Bicuculline
keywords: Bicuculline; Bicuculline (PubChem CID: 10237); Diazepam (PubChem CID: 3016); GABA; GABA (PubChem CID: 119); GABA(A) receptors; Inflammatory pain; L-655,708; L-655,708 (PubChem CID: 5311203); Muscimol (PubChem CID: 4266); Phenobarbital (PubChem CID: 4763); α(5) Subunit-containing GABA(A) receptors