GINIP, a Gαi-Interacting Protein, Functions as a Key Modulator of Peripheral GABAB Receptor-Mediated Analgesia - Cortical Network and Neurovascular Access content directly
Journal Articles Neuron Year : 2014

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

Michael Deage
  • Function : Author
Charline Kambrun
  • Function : Author
Sarah A Low
  • Function : Author
Bertrand Lambolez
Yves Le Feuvre
Emmanuel Bourinet

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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hal-01071132 , version 1 (23-11-2018)

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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, 2014, 84 (1), pp.123-136. ⟨10.1016/j.neuron.2014.08.056⟩. ⟨hal-01071132⟩
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