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

Stéphanie Venteo (1) , Sophie Laffray (2) , Christiane Wetzel (3) , Cyril Rivat (1) , Frédérique Scamps (1) , Ilana Mechaly (1) , Luc Bauchet (1, 4) , Cedric Raoul (1) , Emmanuel Bourinet (2) , Gary R. Lewin (3) , Patrick Carroll (1) , Alexandre Pattyn (1)

1 INM - Institut des Neurosciences de Montpellier
2 IGF - Institut de Génomique Fonctionnelle
3 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
4 Service de Neurochirurgie [CHRU Montpellier]

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 Adelta-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 Adelta- 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.

Domaines: Neurobiologie

Stéphanie Venteo, Sophie Laffray, Christiane Wetzel, Cyril Rivat, Frédérique Scamps, et al.. Fxyd2 regulates Adelta- and C-fiber mechanosensitivity and is required for the maintenance of neuropathic pain. Scientific Reports, 2016, 6, pp.36407. ⟨10.1038/srep36407⟩. ⟨hal-01940962⟩