Abstract：
Chronic pain is a common and challenging clinical problem that significantly impacts patients\' quality of life. The sodium channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect, making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain.
摘要：
慢性疼痛是一个常见且具有挑战性的临床问题，严重影响患者的生活质量。钠通道Nav1.8在慢性疼痛的发生发展中起着至关重要的作用,使其成为治疗慢性疼痛的关键目标之一。在这篇文章中,我们将虚拟筛选与细胞膜层析技术相结合，建立了一种快速高通量筛选Nav1.8选择性抑制剂的新方法。使用这种方法，我们鉴定了一种小分子化合物6,其不仅表现出对Nav1.8的高亲和力和抑制活性,而且还表现出对CFA诱导的慢性炎性疼痛的显著抑制作用。与阳性药物VX-150相比，化合物6显示出更长时间的镇痛作用，使其成为具有潜在临床应用的Nav1.8抑制剂的有希望的候选物。这一发现为慢性疼痛的治疗提供了新的治疗选择。
