Pharmacologically enabling the degradation of Na V 1.8 channels to reduce neuropathic pain.

ABSTRACT:

Abstract

In phase II clinical trials, Na V 1.8 channels were identified as viable targets to treat acute pain. Results were modest, however, and Na V 1.8 pore blockers must be given systemically, potentially leading to adverse effects, especially during prolonged use. A local, long-lasting approach is desirable, yet local anesthetics are neither specific nor long-lasting. In lieu of a pore blocker approach, we show a pharmacological method targeting the scaffolding and degradation of Na V 1.8 channels, which attenuated neuropathic pain behavior in mice. Na V 1.8 channels interact with the WW domain-containing scaffold protein called Magi-1. WW domains are typically found in ubiquitin ligases, and Na V 1.8 channels are susceptible to degradation by ubiquitin ligases. Here, we show N

SUBMITTER: Martin MK 

PROVIDER: S-EPMC12003070 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature