• 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, and Aziz Moqrich.
• Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
• Neuron. 2014 Oct 1;84(1):123-36.

AbstractOne 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.

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