Channelpedia

PubMed 25679765


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPV , TRPV1



Title: GABA blocks pathological but not acute TRPV1 pain signals.

Authors: Christina Hanack, Mirko Moroni, Wanessa C Lima, Hagen Wende, Marieluise Kirchner, Lisa Adelfinger, Katrin Schrenk-Siemens, Anke Tappe-Theodor, Christiane Wetzel, P Henning Kuich, Martin Gassmann, Dennis Roggenkamp, Bernhard Bettler, Gary R Lewin, Matthias Selbach, Jan Siemens

Journal, date & volume: Cell, 2015 Feb 12 , 160, 759-70

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25679765


Abstract
Sensitization of the capsaicin receptor TRPV1 is central to the initiation of pathological forms of pain, and multiple signaling cascades are known to enhance TRPV1 activity under inflammatory conditions. How might detrimental escalation of TRPV1 activity be counteracted? Using a genetic-proteomic approach, we identify the GABAB1 receptor subunit as bona fide inhibitor of TRPV1 sensitization in the context of diverse inflammatory settings. We find that the endogenous GABAB agonist, GABA, is released from nociceptive nerve terminals, suggesting an autocrine feedback mechanism limiting TRPV1 sensitization. The effect of GABAB on TRPV1 is independent of canonical G protein signaling and rather relies on close juxtaposition of the GABAB1 receptor subunit and TRPV1. Activating the GABAB1 receptor subunit does not attenuate normal functioning of the capsaicin receptor but exclusively reverts its sensitized state. Thus, harnessing this mechanism for anti-pain therapy may prevent adverse effects associated with currently available TRPV1 blockers.