Lai Josephine, Porreca Frank, Hunter John C, Gold Michael S
Departments of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA.
Annu Rev Pharmacol Toxicol. 2004;44:371-97. doi: 10.1146/annurev.pharmtox.44.101802.121627.
Physiological and pharmacological evidence both have demonstrated a critical role for voltage-gated sodium channels (VGSCs) in many types of chronic pain syndromes because these channels play a fundamental role in the excitability of neurons in the central and peripheral nervous systems. Alterations in function of these channels appear to be intimately linked to hyperexcitability of neurons. Many types of pain appear to reflect neuronal hyperexcitability, and importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain. This review focuses on the role of VGSCs in the hyperexcitability of sensory primary afferent neurons and their contribution to the inflammatory or neuropathic pain states. The discrete localization of the tetrodotoxin (TTX)-resistant channels, in particular NaV1.8, in the peripheral nerves may provide a novel opportunity for the development of a drug targeted at these channels to achieve efficacious pain relief with an acceptable safety profile.
生理学和药理学证据均已证明电压门控钠通道（VGSCs）在多种慢性疼痛综合征中起关键作用，因为这些通道在中枢和外周神经系统神经元的兴奋性中起基本作用。这些通道功能的改变似乎与神经元的过度兴奋密切相关。许多类型的疼痛似乎反映了神经元的过度兴奋，重要的是，使用依赖性钠通道阻滞剂对多种慢性疼痛有效。本综述重点关注VGSCs在感觉初级传入神经元过度兴奋中的作用及其对炎症性或神经性疼痛状态的影响。河豚毒素（TTX）抗性通道，特别是NaV1.8，在外周神经中的离散定位可能为开发针对这些通道的药物提供新机会，以实现有效缓解疼痛并具有可接受的安全性。
