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Nav1.8，一种非致幻性植物大麻素的镇痛靶点。

Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids.

作者信息

Ghovanloo Mohammad-Reza, Tyagi Sidharth, Zhao Peng, Waxman Stephen G

机构信息

Department of Neurology, Yale School of Medicine, New Haven, CT 06520.

Center for Neuroscience and Regeneration Research, Yale University, West Haven, CT 06516.

出版信息

Proc Natl Acad Sci U S A. 2025 Jan 28;122(4):e2416886122. doi: 10.1073/pnas.2416886122. Epub 2025 Jan 21.

DOI:10.1073/pnas.2416886122
PMID:39835903
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11789019/
Abstract

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

摘要

疼痛影响着全球数十亿人，但治疗选择有限且存在一系列不良反应。对安全且无成瘾性疼痛治疗方法的探索促使人们将重点放在伤害感受器兴奋性的关键介质上。外周神经系统中的电压门控钠（Nav）通道——Nav1.7、Nav1.8和Nav1.9——在疼痛信号传导中起关键作用。其中，Nav1.8因其从失活中快速恢复的能力以及在重复放电中的作用而显示出前景，最近的临床研究提供了原理证明，即阻断Nav1.8可减轻人类疼痛。我们在此报告，三种非致幻性大麻素——大麻二酚（CBD）、大麻萜酚（CBG）和大麻酚（CBN）——可有效抑制Nav1.8，表明它们作为镇痛化合物的潜力。特别是，CBG因其有效抑制外周感觉神经元兴奋性的能力而显示出巨大前景。这些发现突出了大麻素，尤其是CBG，作为可能通过阻断Nav1.8减轻疼痛的药物的治疗潜力，值得进一步进行体内研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/acd40673eda7/pnas.2416886122fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/7838e6e29249/pnas.2416886122fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/ac257dd3bddd/pnas.2416886122fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/1be97e6269e1/pnas.2416886122fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/2ed9ae2e3246/pnas.2416886122fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/9fd83d8ed411/pnas.2416886122fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/acd40673eda7/pnas.2416886122fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/7838e6e29249/pnas.2416886122fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/ac257dd3bddd/pnas.2416886122fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/1be97e6269e1/pnas.2416886122fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/2ed9ae2e3246/pnas.2416886122fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/9fd83d8ed411/pnas.2416886122fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8b/11789019/acd40673eda7/pnas.2416886122fig06.jpg

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