背根神经节（DRG）是负责将外周疼痛信号传递到中枢神经系统的主要神经元，在疼痛传导中发挥着至关重要的作用。调节 DRG 兴奋性被认为是疼痛管理的可行方法。神经元兴奋性与神经元上的离子通道有着复杂的联系。中小型DRG神经元主要参与疼痛传导，具有高水平的TTX-S钠通道，其中Nav1.7约占目前的80%。电压门控钠通道（VGSC 或 Nav）阻滞剂是治疗中枢神经系统疾病（尤其是慢性疼痛）的重要靶点。 VGSC 在控制细胞兴奋性方面发挥着关键作用。临床研究表明，Nav1.7 在痛觉中发挥着至关重要的作用，并且有强有力的遗传证据将 Nav1.7 及其编码基因 SCN9A 基因与人类疼痛性疾病联系起来。许多研究表明 Nav1.7 在疼痛管理中发挥着重要作用。 Nav1.7 在疼痛信号通路中的作用使其成为新型止痛药潜在开发的有吸引力的靶点。同时，了解Nav1.7的架构可能有助于开发下一代止痛药。这篇综述提供了最近报道的针对 Nav1.7 通路的分子抑制剂的最新情况，总结了它们的构效关系 (SAR)，并讨论了它们对疼痛疾病的治疗作用。药物化学家正在努力提高Nav1.7抑制剂的治疗指数，实现更好的镇痛效果，并减少副作用。我们希望这篇综述将有助于开发新型 Nav1.7 抑制剂作为潜在药物。版权所有 © 2024。由 Elsevier Inc. 出版。

The dorsal root ganglion (DRG) is the primary neuron responsible for transmitting peripheral pain signals to the central nervous system and plays a crucial role in pain transduction. Modulation of DRG excitability is considered a viable approach for pain management. Neuronal excitability is intricately linked to the ion channels on the neurons. The small and medium-sized DRG neurons are chiefly engaged in pain conduction and have high levels of TTX-S sodium channels, with Nav1.7 accounting for approximately 80% of the current. Voltage-gated sodium channel (VGSC or Nav) blockers are vital targets for the management of central nervous system diseases, particularly chronic pain. VGSCs play a key role in controlling cellular excitability. Clinical research has shown that Nav1.7 plays a crucial role in pain sensation, and there is strong genetic evidence linking Nav1.7 and its encoding gene SCN9A gene to painful disorders in humans. Many studies have shown that Nav1.7 plays an important role in pain management. The role of Nav1.7 in pain signaling pathways makes it an attractive target for the potential development of new pain drugs. Meanwhile, understanding the architecture of Nav1.7 may help to develop the next generation of painkillers. This review provides updates on the recently reported molecular inhibitors targeting the Nav1.7 pathway, summarizes their structure-activity relationships (SARs), and discusses their therapeutic effects on painful diseases. Pharmaceutical chemists are working to improve the therapeutic index of Nav1.7 inhibitors, achieve better analgesic effects, and reduce side effects. We hope that this review will contribute to the development of novel Nav1.7 inhibitors as potential drugs.Copyright © 2024. Published by Elsevier Inc.