Small molecules targeting sodium and calcium channels for neuropathic pain.

Brian Bear, Juliana Asgian, Andreas Termin, Nicole Zimmermann
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Abstract

Neuropathic pain is a chronic disease, which impacts millions of individuals worldwide. The condition is currently treated with several drugs that provide pain relief that is inconsistent and complicated by CNS or cardiovascular (CV) side effects. Voltage-gated sodium channels (VGSCs) and voltage-gated calcium channels (VGCCs) are of particular interest as targets for neuropathic pain because they control electrical signals in both the central and peripheral nervous system. Recent research has demonstrated that the expression of voltage-gated ion channels changes significantly under conditions of neuropathic pain in rodents and humans. Selective modulation of the channels involved in the pathology of the disease, while sparing the channels that are essential for normal nociception, offers promising opportunities for therapeutic intervention. This review summarizes recent developments of small molecules that target VGSCs and VGCCs.

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靶向钠钙通道的小分子治疗神经性疼痛。
神经性疼痛是一种慢性疾病,影响着全世界数百万人。目前有几种缓解疼痛的药物治疗此病,但这些药物不一致,并伴有中枢神经系统或心血管(CV)副作用。电压门控钠通道(VGSCs)和电压门控钙通道(VGCCs)作为神经性疼痛的靶点特别有趣,因为它们控制中枢和外周神经系统的电信号。最近的研究表明,在啮齿类动物和人类的神经性疼痛条件下,电压门控离子通道的表达发生了显著变化。选择性调节与疾病病理相关的通道,同时保留正常伤害感觉所必需的通道,为治疗干预提供了有希望的机会。本文综述了近年来靶向VGSCs和VGCCs的小分子研究进展。
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