Targeting Na_v1.7 and Na_v1.8 with a PIKfyve inhibitor to reverse inflammatory and neuropathic pain.

ABSTRACT: PIKfyve (1-phosphatidylinositol 3-phosphate 5-kinase), a lipid kinase, plays an important role in generating phosphatidylinositol (3,5)-bisphosphate (PI(3,5)P₂). SGC-PIKFYVE-1, a potent and selective inhibitor of PIKfyve, has been used as a chemical probe to explore pathways dependent on PIKfyve activity. Based on reported changes in membrane dynamics and ion transport in response to PIKfyve inhibition, we hypothesized that pharmacological inhibition of PIKfyve could modulate pain. Acute treatment with SGC-PIKFYVE-1 (10 µM) inhibited voltage-gated sodium currents through the inhibition of Na_v1.7 and Na_v1.8 channels, without affecting voltage-gated calcium or potassium currents in sensory neurons. Additionally, systemic administration of SGC-PIKFYVE-1 (30 mg

SUBMITTER: Rodriguez-Palma EJ 

PROVIDER: S-EPMC11665415 | biostudies-literature | 2025 Jan-Jun

REPOSITORIES: biostudies-literature