Abstract：
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.
摘要：
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初级神经元，在疼痛转导中起着至关重要的作用。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错综复杂地联系在一起。中小型DRG神经元主要参与疼痛传导，并具有高水平的TTX-S钠通道，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的重要靶点，尤其是慢性疼痛。VGSCs在控制细胞兴奋性中起关键作用。临床研究表明，Nav1.7在疼痛感觉中起着至关重要的作用，并且有强有力的遗传证据将Nav1.7及其编码基因SCN9A基因与人类疼痛疾病联系起来。许多研究表明，Nav1.7在疼痛管理中起着重要作用。Nav1.7在疼痛信号通路中的作用使其成为潜在开发新型疼痛药物的有吸引力的靶标。同时,了解Nav1.7的结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途径的分子抑制剂的最新信息。总结了它们的结构-活性关系(SARs)，并讨论了它们对疼痛疾病的治疗效果。药物化学家正在努力提高Nav1.7抑制剂的治疗指数，达到更好的镇痛效果，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。
