Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids

• 成果类型: Article
• 署名作者: Ghovanloo, Mohammad-Reza; Tyagi, Sidharth; Zhao, Peng; Waxman, Stephen G.
• 署名单位: Yale University; Yale University; Yale University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9930
• DOI: 10.1073/pnas.2416886122
• 发表日期: 2025-01-28
• 关键词: na(v)1.8 sodium-channels; cannabinoid receptor; cannabidiol; pain; inhibition; seizures; electrogenesis; inactivation; nociceptors; expression

摘要

Pain impacts billions of people worldwide, but treatment options are limited and a spectrum of adverse effects. The search for safe and nonaddictive pain treatments led to a focus on key mediators of nociceptor excitability. Voltage- gated sodium channels in the peripheral nervous system-Nav1.7, Nav1.8, and Nav1.9-play cial roles in pain signaling. Among these, Nav1.8 has shown promise due to its recovery from inactivation and role in repetitive firing, with recent clinical studies viding proof- of- principal that block of Nav1.8 can reduce pain in humans. We here that three nonpsychotomimetic cannabinoids-cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN)-effectively inhibit Nav1.8, suggesting their potential analgesic compounds. In particular, CBG shows significant promise due to its ability effectively inhibit excitability of peripheral sensory neurons. These findings highlight therapeutic potential of cannabinoids, particularly CBG, as agents that may attenuate pain via block of Nav1.8, warranting further in vivo studies.