GINIP, a Gαi-Interacting Protein, Functions as a Key Modulator of Peripheral GABAB Receptor-Mediated Analgesia

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.
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Neuron, Elsevier, 2014, 84 (1), pp.123-136. 〈10.1016/j.neuron.2014.08.056〉
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Soumis le : vendredi 23 novembre 2018 - 15:13:40
Dernière modification le : lundi 10 décembre 2018 - 01:25:09

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Stéphane Gaillard, Laure Lo Re, Annabelle Mantilleri, Régine Hepp, Louise Urien, et al.. GINIP, a Gαi-Interacting Protein, Functions as a Key Modulator of Peripheral GABAB Receptor-Mediated Analgesia. Neuron, Elsevier, 2014, 84 (1), pp.123-136. 〈10.1016/j.neuron.2014.08.056〉. 〈hal-01071132〉

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