GINIP, a Gαi-Interacting protein, functions as a key modulator of peripheral GABAB receptor-mediated analgesia

Stéphane Gaillard, Laure Lo Re, Annabelle Mantilleri, Régine Hepp, Louise Urien, Pascale Malapert, Serge Alonso, Michael Deage, Charline Kambrun, Marc Landry, Sarah A. Low, Abdelkrim Alloui, Bertrand Lambolez, Grégory Scherrer, Yves Le Feuvre, Emmanuel Bourinet, Aziz Moqrich
Neuron. 2014-10-01; 84(1): 123-136
DOI: 10.1016/j.neuron.2014.08.056

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1. Neuron. 2014 Oct 1;84(1):123-136. doi: 10.1016/j.neuron.2014.08.056. Epub 2014
Sep 18.

GINIP, a Gαi-interacting protein, functions as a key modulator of peripheral
GABAB receptor-mediated analgesia.

Gaillard S(1), Lo Re L(1), Mantilleri A(1), Hepp R(2), Urien L(1), Malapert P(1),
Alonso S(1), Deage M(3), Kambrun C(4), Landry M(4), Low SA(5), Alloui A(6),
Lambolez B(2), Scherrer G(5), Le Feuvre Y(4), Bourinet E(3), Moqrich A(7).

Author information:
(1)Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de
Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
(2)Sorbonne Universités, UPMC Univ Paris 06, UM CR 18, Neuroscience Paris Seine,
75005 Paris, France; Centre National de la Recherche Scientifique (CNRS), UMR
8246 Paris, France; Institut national de la Santé et de la Recherche Médicale
(INSERM), UMR-S 1130 Paris, France.
(3)Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de
Génomique Fonctionnelle, UMR 5203, CNRS, U661, INSERM, Universités Montpellier
I&II, 141 Rue de la Cardonille, 34094 Montpellier Cedex 05, France.
(4)University Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297,
33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France.
(5)Department of Anesthesiology, Perioperative and Pain Medicine, Department of
Molecular and Cellular Physiology, Stanford Neurosciences Institute, Stanford
University, Palo Alto, CA 94304, USA.
(6)Laboratoire de Pharmacologie Médicale, Faculté de Médecine et de Pharmacie,
UMR 766 INSERM, 28 place Henri-Dunant, BP 38, 63001 Clermont-Ferrand Cedex 1,
France.
(7)Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de
Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France. Electronic
address: .

One feature of neuropathic pain is a reduced GABAergic inhibitory function.
Nociceptors have been suggested to play a key role in this process. However, the
mechanisms behind nociceptor-mediated modulation of GABA signaling remain to be
elucidated. Here we describe the identification of GINIP, a Gαi-interacting
protein expressed in two distinct subsets of nonpeptidergic nociceptors. GINIP
null mice develop a selective and prolonged mechanical hypersensitivity in models
of inflammation and neuropathy. GINIP null mice show impaired responsiveness to
GABAB, but not to delta or mu opioid receptor agonist-mediated analgesia
specifically in the spared nerve injury (SNI) model. Consistently,
GINIP-deficient dorsal root ganglia neurons had lower baclofen-evoked inhibition
of high-voltage-activated calcium channels and a defective presynaptic inhibition
of lamina IIi interneurons. These results further support the role of
unmyelinated C fibers in injury-induced modulation of spinal GABAergic inhibition
and identify GINIP as a key modulator of peripherally evoked GABAB-receptors
signaling.

Copyright © 2014 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.neuron.2014.08.056
PMCID: PMC7348640
PMID: 25242222 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus