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Fxyd2 regulates Aδ- and C-fiber mechanosensitivity and is required for the maintenance of neuropathic pain

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Item Type:Article
Title:Fxyd2 regulates Aδ- and C-fiber mechanosensitivity and is required for the maintenance of neuropathic pain
Creators Name:Ventéo, S. and Laffray, S. and Wetzel, C. and Rivat, C. and Scamps, F. and Méchaly, I. and Bauchet, L. and Raoul, C. and Bourinet, E. and Lewin, G.R. and Carroll, P. and Pattyn, A.
Abstract:Identification of the molecular mechanisms governing sensory neuron subtype excitability is a key requisite for the development of treatments for somatic sensory disorders. Here, we show that the Na,K-ATPase modulator Fxyd2 is specifically required for setting the mechanosensitivity of Aδ-fiber low-threshold mechanoreceptors and sub-populations of C-fiber nociceptors, a role consistent with its restricted expression profile in the spinal somatosensory system. We also establish using the spared nerve injury model of neuropathic pain, that loss of Fxyd2 function, either constitutively in Fxyd2(-/-) mice or acutely in neuropathic rats, efficiently alleviates mechanical hypersensitivity induced by peripheral nerve lesions. The role of Fxyd2 in modulating Aδ- and C-fibers mechanosensitivity likely accounts for the anti-allodynic effect of Fxyd2 knockdown. Finally, we uncover the evolutionarily conserved restricted expression pattern of FXYD2 in human dorsal root ganglia, thus identifying this molecule as a potentially promising therapeutic target for peripheral neuropathic pain management.
Keywords:Animal Disease Models, Electron Microscopy, In Situ Hybridization, Locomotion, Mechanoreceptors, Nerve Fibers, Neuralgia, Nociceptors, Patch-Clamp Techniques, RNA Interference, Sensory Receptor Cells, Small Interfering RNA, Sodium-Potassium-Exchanging ATPase, Spinal Ganglia, Animals, Mice, Rats
Source:Scientific Reports
ISSN:2045-2322
Publisher:Nature Publishing Group (U.K.)
Volume:6
Page Range:36407
Date:2 November 2016
Official Publication:https://doi.org/10.1038/srep36407
PubMed:View item in PubMed

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