Central sensitisation in the dorsal horn regulates the chronicity of pain, resulting in pain hypersensitivity. We recently found that the astroglial inward rectifier potassium Kir4.1 channels are drastically down regulated in the dorsal horn during inflammatory chronic trigeminal pain and showed this is sufficient and necessary to underlie pain.
We now wish to investigate whether similar changes in Kir4.1 relate to one of the most frequent and disabling chronic pain condition involving the trigeminal system: chronic migraine, and unravel the mechanisms by which down-regulation of central astrocyte Kir4.1 leads to pain.
The questions will be investigated through a combination of state of the art approaches such as selective, virally mediated, targeting of Kir4.1 expression in the central nervous system, combined with transcriptomics and multiple, morphological, biochemical, molecular, pharmacological, electrophysiological, cell imaging and behavioural techniques in an animal model of chronic migraine, while Kir4.1 expression will be measured in human brain samples.
Results will provide foundations for a mechanistic understanding of the role of astrocytes in central sensitisation, which should lead to translational opportunities. Through this project, we aim to discover the therapeutic potential of targeting central Kir4.1 channels to treat chronic pain.
The thesis will be conducted under the supervision of Dr. Radhouane DALLEL (PU/PH-HDR), in the Neuro-Dol laboratory (UMR INSERM/UCA U1107)
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