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Rôle des canaux calciques Cav3.2 dans les interneurones de la lamina II de la moelle épinière

Abstract : Acute pain is essential for survival, but chronic pain is often invalidating. Prolonged pain states are one of the first causes of medical consultation, and they are experienced by as much as 20% of the population. However, our current analgesics are not fully reliable in alleviating chronic pains, with low beneficial/risk ratio. Thus, finding new pharmacological agents are a primordial objective. A better understanding of pain networks is necessary.Several studies have suggested that the T-type calcium channel, Cav3.2, might be a promising target for analgesics. Indeed, Cav3.2 is expressed all along pain pathways, both within the peripheral nociceptive track and within the central nervous system. Interestingly, Cav3.2 is strongly express in the dorsal horn of the spinal cord, which is the first relay for pain processing. Furthermore, thanks to their activation near resting potentials, Cav3.2 channels fit well in regulating neuronal excitability and synaptic integration.In this thesis, we have analyzed Cav3.2 expression in dorsal horn interneurons. Our results show that Cav3.2 is expressed in different types of interneurons (~60%), mostly excitatory, but also inhibitory. Interestingly, all PKCγ neurons, involved in mechanical allodynia, expressed Cav3.2. We then used a viral approach to label and study electrophysiological properties of Cav3.2-expressing neurons, and also to specifically delete this channel in the lumbar spinal cord. Our results show that Cav3.2 is involved in subthreshold depolarizations, in the properties of the action potentials and in the firing patterns of these neurons. Thus, Cav3.2 might play an important role in pain states at the spinal cord level, characterized by neuronal excitability alterations.
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Submitted on : Monday, January 15, 2018 - 12:35:06 PM
Last modification on : Tuesday, September 8, 2020 - 4:04:47 AM
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Miriam Candelas. Rôle des canaux calciques Cav3.2 dans les interneurones de la lamina II de la moelle épinière. Médecine humaine et pathologie. Université Montpellier, 2017. Français. ⟨NNT : 2017MONTT027⟩. ⟨tel-01684274⟩

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