Modulation of SK Channels via Calcium Buffering Tunes Intrinsic Excitability of Parvalbumin Interneurons in Neuropathic Pain: A Computational and Experimental Investigation

Parvalbumin-expressing interneurons (PVINs) in the spinal cord prevent touch inputs from activating pain circuits. Nerve injury decreases the output of these PVINs, contributing to neuropathic pain. This study uses a computational model and experiments to show that after nerve injury, PVINs change their firing pattern due to increased activity of SK channels, which are influenced by impaired calcium buffering. The findings suggest that SK channels could be potential therapeutic targets for treating neuropathic pain by restoring the normal function of PVINs.

• 1
  Nerve injury induces a change in PVIN firing patterns from tonic to adaptive in male mice.
• 2
  Computational modeling predicts that increased contribution of SK channels, enabled by impairment in intracellular calcium buffering systems, causes this firing pattern transition.
• 3
  Experimental validation shows that pharmacological modulation of SK channels can reverse the firing pattern changes in PVINs from both naive and nerve-injured mice.