Small molecule targeting Na V 1.7 via inhibition of CRMP2-Ubc9 interaction reduces pain-related outcomes in a rodent osteoarthritic model.

ABSTRACT:

Abstract

Osteoarthritis (OA) is a highly prevalent and disabling joint disease, characterized by pathological progressive joint deformation and clinical symptoms of pain. Disease-modifying treatments remain unavailable, and pain-mitigation is often suboptimal, but recent studies suggest beneficial effects by inhibition of the voltage-gated sodium channel Na V 1.7. We previously identified compound 194 as an indirect inhibitor of Na V 1.7 by preventing SUMOylation of the Na V 1.7-trafficking protein, collapsin response mediator protein 2. Compound 194 reduces the functional activity of Na V 1.7 channels and produces effective analgesia in a variety of acute and neuropathic pain models. However, its effectiveness has not yet been evaluated in models of OA. Here, we explore the effect

SUBMITTER: Hestehave S 

PROVIDER: S-EPMC11649477 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature