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Analyse mécanistique des traitements de la douleur neuropathique

Abstract : Neuropathic pain is caused by a lesion or a disease of the somatosensory nervous system. Pregabalin, an anticonvulsant, and duloxetine, an antidepressant, are the standard treatments, effective in one-third of patients. A better understanding of their mechanisms of action is a crucial point to improve their tolerance and efficiency. By using a murine model of peripheral neuropathy, we have shown that : 1) pregabalin, whose effect is independent from the opioid system, acts on the peripheral neuroimmune component of pain ; 2) duloxetine acts via two independent mechanisms, one central (descending controls) for an acute treatment and the other peripheral (dorsal root ganglia) for a chronic treatment. In this case, transcriptomic analysis hightlights an inhibition of the neurogenic inflammation. Comparison of duloxetine plasmatic levels in humans and mice suggests a peripheral action in humans.
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Mélanie Kremer. Analyse mécanistique des traitements de la douleur neuropathique. Neurobiologie. Université de Strasbourg, 2016. Français. ⟨NNT : 2016STRAJ033⟩. ⟨tel-02003411⟩

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