GABA Blocks Pathological but Not Acute TRPV1 Pain Signals | Zendy

Christina Hanack | Zendy; Mirko Moroni | Zendy; Wanessa C Lima | Zendy; Hagen Wende | Zendy; Marieluise Kirchner | Zendy; Lisa Adelfinger | Zendy; Katrin Schrenk-Siemens | Zendy; Anke TappeTheodor | Zendy; Christiane Wetzel | Zendy; P. Henning J. L. Kuich | Zendy; Martin Gassmann | Zendy; Dennis Roggenkamp | Zendy; Bernhard Bettler | Zendy; Gary R. Lewin | Zendy; Matthias Selbach | Zendy; Jan Siemens | Zendy

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GABA Blocks Pathological but Not Acute TRPV1 Pain Signals

Author(s) -

Christina Hanack,

Mirko Moroni,

Wanessa C Lima,

Hagen Wende,

Marieluise Kirchner,

Lisa Adelfinger,

Katrin Schrenk-Siemens,

Anke TappeTheodor,

Christiane Wetzel,

P. Henning J. L. Kuich,

Martin Gassmann,

Dennis Roggenkamp,

Bernhard Bettler,

Gary R. Lewin,

Matthias Selbach,

Jan Siemens

Publication year - 2015

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2015.01.022

Subject(s) - trpv1 , biology , context (archaeology) , gabab receptor , sensitization , protein subunit , pharmacology , agonist , receptor , neuroscience , transient receptor potential channel , microbiology and biotechnology , biochemistry , paleontology , gene

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.

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