title: The α5 subunit containing GABAA receptors contribute to chronic pain.
abstract: It has been recently proposed that α5-subunit containing GABAA receptors (α5-GABAA receptors) that mediate tonic inhibition might be involved in pain. The purpose of this study was to investigate the contribution of α5-GABAA receptors in the loss of GABAergic inhibition and in formalin-induced, complete Freund's adjuvant (CFA)-induced and L5 and L6 spinal nerve ligation-induced long-lasting hypersensitivity. Formalin or CFA injection and L5 and L6 spinal nerve ligation produced long-lasting allodynia and hyperalgesia. Moreover, formalin injection impaired the rate-dependent depression of the Hofmann reflex. Peripheral and intrathecal pretreatment or post-treatment with the α5-GABAA receptor antagonist, L-655,708 (0.15-15 nmol), prevented and reversed, respectively, these long-lasting behaviors. Formalin injection increased α5-GABAA receptor mRNA expression in the spinal cord and dorsal root ganglia (DRG) mainly at 3 days. The α5-GABAA receptors were localized in the dorsal spinal cord and DRG colabeling with NeuN, CGRP, and IB4 which suggests their presence in peptidergic and nonpeptidergic neurons. These receptors were found mainly in small and medium sized neurons. Formalin injection enhanced α5-GABAA receptor fluorescence intensity in spinal cord and DRG at 3 and 6 days. Intrathecal administration of L-655,708 (15 nmol) prevented and reversed formalin-induced impairment of rate-dependent depression. These results suggest that α5-GABAA receptors play a role in the loss of GABAergic inhibition and contribute to long-lasting secondary allodynia and hyperalgesia.
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, México, DF, Mexico Neuroregeneration Laboratory, Department of Anesthesiology, University of California San Diego, La Jolla, CA, USA Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados, México, DF, Mexico Departamento de Biología Molecular e Histocompatibilidad, Hospital General "Dr. Manuel Gea González," México, DF, Mexico Department of Pathology, University of California San Diego, La Jolla, CA, USA Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, México, DF, Mexico Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia.
authors.forename: Mariana
authors.initials: M
authors.lastname: Bravo-Hernández
authors.forename: José A
authors.initials: JA
authors.lastname: Corleto
authors.forename: Paulino
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.forename: Ricardo
authors.initials: R
authors.lastname: González-Ramírez
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Pineda-Farias
authors.forename: Ricardo
authors.initials: R
authors.lastname: Felix
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Calcutt
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Delgado-Lezama
authors.forename: Martin
authors.initials: M
authors.lastname: Marsala
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology; D007093:Imidazoles / Q000008:administration & dosage; D007278:Injections, Spinal; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D021122:Protein Subunits / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D005464:Fluorobenzenes; C511535:Gabra5 protein, rat; D007093:Imidazoles; C105490:L 655,708; D021122:Protein Subunits; D011963:Receptors, GABA-A; D014230:Triazoles; C409903:L 838,417