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Traitement d'une douleur neuropathique par la modulation pharmacologique du complexe basolatéral de l'amygdale

Abstract : The amygdala is a major control center of the emotions, but also integrates sensory, especially nociceptive information. Cortical afferents to the amygdala largely target its basolateral complex. The basolateral amygdala (BLA) then projects to the central amygdala nucleus, which in turn projects densely to the periaqueductal gray and thus can drive a behavioural output via the spinal cord. Data obtained during my thesis have shown that the balance between excitation and inhibition in the BLA triggers an tonic control of pain. Therefore modulating one of the neurotransmission directly influences the pain threshold of control or nociceptive mice. My thesis work also focused on the functioning of an anxiolytic and non benzodiazepinic drug ; Etifoxin (EFX). This molecule as a positive modulator of GABAA receptors and indirectly by increasing the synthesis of neurosteroids, also known as strong modulator of these receptors. In our team, we already showed that EFX has anti-nociceptive effects when injected intraperitonealy in rats. Here we wanted to determine the action of EFX on pain descending control drive by BLA. We showed that EFX infusion in the BLA seems to be anti-nociceptive, inducing a recover of the pre-cuff mechanical threshold level. We also used a patch-clamp approach to study directly in vitro the modulation of the inhibitory synaptic transmission produced by EFX. We showed that EFX potentiate the inhibition in BLA neurons via different and complementary mechanisms. These potentiating effects are mostly dependent of a neurosteroidogenesis increase.
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https://tel.archives-ouvertes.fr/tel-01149108
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Submitted on : Wednesday, May 6, 2015 - 12:47:05 PM
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Alexandre Zeitler. Traitement d'une douleur neuropathique par la modulation pharmacologique du complexe basolatéral de l'amygdale. Neurosciences [q-bio.NC]. Université de Strasbourg, 2013. Français. ⟨NNT : 2013STRAJ115⟩. ⟨tel-01149108⟩

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