Two pore domain THIK2 channel is involved in acute and chronic pain signal regulation

Gilbert, N.; Chatelain, F. C.; Gibaud, S.; Lorivel, T.; Shen, Y.-L.; kerros, M.-E.; Feliciangeli, S.; Fiore, F.; Chen, C.-C.; Lesage, F.; Delphine, B.

doi:10.1101/2025.08.08.669258

bioRxiv · 10.1101/2025.08.08.669258

Two pore domain THIK2 channel is involved in acute and chronic pain signal regulation

Gilbert, N.·Chatelain, F. C.·Gibaud, S.·Lorivel, T.·Shen, Y.-L.·kerros, M.-E.·Feliciangeli, S.·Fiore, F.·Chen, C.-C.·Lesage, F.·Delphine, B.

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Abstract

Two-pore domain potassium channels (K2P) regulate neuronal excitability by acting as hyperpolarizing leak channels. Among them, THIK2 remain poorly characterized. Although no study has yet clearly linked them to excitability or pain, their selective expression in nociceptive neurons of the Dorsal Root Ganglia (DRG) suggests a role in nociception and pain regulation. This project investigates THIK2 channels in pain pathophysiology through molecular, electrophysiological, and behavioral approaches. We mapped THIK expression patterns and in THIK2 knock-out mice, we examined DRG neuron excitability and pain sensitivity. Results reveal thermal hypersensitivity under both naive and inflammatory conditions, indicating that THIK2 normally limits neuronal hyperexcitability. These findings position THIK2 as a potential therapeutic target in chronic inflammatory pain, with peripheral inhibition potentially offering analgesia without central opioid side effects.

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Gilbert, N., Chatelain, F. C., Gibaud, S., Lorivel, T., Shen, Y.-L., kerros, M.-E., Feliciangeli, S., Fiore, F., Chen, C.-C., Lesage, F., Delphine, B.. 2025-08-12. Two pore domain THIK2 channel is involved in acute and chronic pain signal regulation. https://doi.org/10.1101/2025.08.08.669258

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