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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.

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: aziz.moqrich@univ-amu.fr.

Abstract

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.

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