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Updated: Aug 22, 2026

Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
Two pore domain THIK2 potassium channels regulate acute and chronic pain signaling
Nicolas Gilbert1,2, Franck C Chatelain1,2, Solène Gibaud1
1Université Côte d'Azur, CNRS, Inserm, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Valbonne, France.
Introduction:
Two-pore domain potassium channels regulate neuronal excitability by generating background potassium currents that stabilize the resting membrane potential. Although several two-pore domain potassium channels have been implicated in pain signaling, the physiological role of tandem pore domain halotane-inhibited K+ channel (THIK2) remains largely unknown despite its high expression in human and mouse nociceptive dorsal root ganglion (DRG) neurons.
Objective:
This study aimed to determine the cellular distribution of THIK2 in sensory neurons and to investigate its contribution to neuronal excitability and nociceptive processing under physiological and inflammatory conditions.
Methods:
We combined molecular analyses, electrophysiological recordings, and behavioral approaches. THIK1 and THIK2 expression patterns were mapped in mouse DRGs. Whole-cell electrophysiology was used to assess membrane excitability in sensory neurons from wild-type and THIK2-/- knockout mice. Behavioral tests evaluated thermal sensitivity under naive and inflammatory conditions.
Results:
We provide the first comprehensive characterization of THIK1 and THIK2 expression in mouse DRG. THIK2 deletion increased neuronal firing during sustained stimulation, indicating a loss of tonic inhibitory control of membrane excitability, particularly in nonpeptidergic IB4-positive C-fiber neurons. Behaviorally, THIK2-/- mice displayed marked thermal hypersensitivity at baseline and during inflammation, consistent with enhanced sensory neuron hyperexcitability.
Conclusion:
THIK2 channels act as key regulators preventing pathological hyperexcitability in nociceptive sensory neurons. Their loss leads to increased neuronal firing and enhanced thermal sensitivity, identifying THIK2 as a promising therapeutic target for chronic inflammatory pain.
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