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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., Laffray, S., Wetzel, C., Rivat, C., Scamps, F., Méchaly, I., Bauchet, L., Raoul, C., Bourinet, E., Lewin, G.R., 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 |
| 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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