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Contribution des canaux calciques de type T supra-spinaux à la douleur neuropathique : rôle du canal Cav3.2 exprimé dans le noyau prétectal antérieur

Abstract : Current treatments of neuropathies are inadequate. It is necessary to identify new therapeutical targets. Cav3.2 isoform of T-type calcium channels is a good candidate, considering its role in acute and neuropathic pain perception, established at the peripheral and spinal level. However, the role of Cav3.2 in the supra-spinal treatment of pain signals remains elusive. To address this question, we used the mouse line KI-Cav3.2-eGFPflox allowing localization of Cav3.2 thanks to an inserted GFP, and its specific deletion thanks to loxP sites. Cav3.2 was expressed in parvalbumin (PV) neurons of the Anterior Pretectal Nucleus (APN). APN is a crossroad of connectivity of the somatosensory system implicated in pain perception. Therefore we studied the impact of Cav3.2 expressed in this region on basal and neuropathic somatosensory perception. We tested the sensitivity of mice deleted for Cav3.2 in this region, before and after spared nerve injury. This deletion does not seem to affect basal sensitivity but significantly reduces the development of neuropathic pain. In vitro recordings and molecular analysis of PV neurons of the APN shows that those co-expressing Cav3.2 are GABAergic. Moreover, these neurons project to the thalamus, zona incerta and medulla. Together, these results suggest that APN could exert a descending and/or ascending inhibitory control on somatosensory system. The network excitability would critically depend on Cav3.2 activity during the development of neuropathy.
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Sophie Fayad. Contribution des canaux calciques de type T supra-spinaux à la douleur neuropathique : rôle du canal Cav3.2 exprimé dans le noyau prétectal antérieur. Neurosciences. Sorbonne Université, 2019. Français. ⟨NNT : 2019SORUS102⟩. ⟨tel-02978832⟩

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