The ?5 subunit-containing GABAA receptors contribute to chronic pain.
Pain. 2015 Nov 5;
Authors: Bravo-Hernández M, Corleto JA, Barragán-Iglesias P, González-Ramírez R, Pineda-Farias JB, Felix R, Calcutt NA, Delgado-Lezama R, Marsala M, Granados-Soto V
It has been recently proposed that ?5-subunit containing GABAA receptors (?5-GABAA receptors) that mediate tonic inhibition might be involved in pain. The purpose of this study was to investigate the contribution of ?5-GABAA receptors in the loss of GABAergic inhibition and in formalin-, Complete Freund’s adjuvant (CFA)- and L5/L6 spinal nerve ligation-induced long-lasting hypersensitivity. Formalin or CFA injection and L5/L6 spinal nerve ligation produced long-lasting allodynia and hyperalgesia. Moreover, formalin injection impaired the rate-dependent depression (RDD) of the Hofmann reflex. Peripheral and intrathecal pre-treatment or post-treatment with the ?5-GABAA receptor antagonist, L-655,708 (0.15-15 nmol) prevented and reversed, respectively, these long-lasting behaviors. Formalin injection increased ?5-GABAA receptors mRNA expression in the spinal cord and dorsal root ganglia (DRG) mainly at 3 days. ?5-GABAA receptors were localized in the dorsal spinal cord and DRG co-labeling with NeuN, CGRP and IB4 suggesting their presence in peptidergic and non-peptidergic neurons. These receptors were found mainly in small- and medium-size neurons. Formalin injection enhanced ?5-GABAA receptors 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 RDD. These results suggest that ?5-GABAA receptors play a role in the loss of GABAergic inhibition and contribute to long-lasting secondary allodynia and hyperalgesia.
PMID: 26545088 [PubMed – as supplied by publisher]