Indiana University School of Medicine, Indianapolis, IN, United States.
Curr Top Membr. 2016;78:599-638. doi: 10.1016/bs.ctm.2015.12.005. Epub 2016 Feb 2.
Pain is a serious health problem that impacts the lives of many individuals. Hyperexcitability of peripheral sensory neurons contributes to both acute and chronic pain syndromes. Because voltage-gated sodium currents are crucial to the transmission of electrical signals in peripheral sensory neurons, the channels that underlie these currents are attractive targets for pain therapeutics. Sodium currents and channels in peripheral sensory neurons are complex. Multiple-channel isoforms contribute to the macroscopic currents in nociceptive sensory neurons. These different isoforms exhibit substantial variations in their kinetics and pharmacology. Furthermore, sodium current complexity is enhanced by an array of interacting proteins that can substantially modify the properties of voltage-gated sodium channels. Resurgent sodium currents, atypical currents that can enhance recovery from inactivation and neuronal firing, are increasingly being recognized as playing potentially important roles in sensory neuron hyperexcitability and pain sensations. Here we discuss unusual sodium channels and currents that have been identified in nociceptive sensory neurons, describe what is known about the molecular determinants of the complex sodium currents in these neurons. Finally, we provide an overview of therapeutic strategies to target voltage-gated sodium currents in nociceptive neurons.
疼痛是一个严重的健康问题，影响着许多人的生活。外周感觉神经元的过度兴奋是导致急性和慢性疼痛综合征的原因之一。由于电压门控钠离子电流对周围感觉神经元中电信号的传递至关重要，因此这些电流所依赖的通道是疼痛治疗的有吸引力的靶点。外周感觉神经元中的钠离子电流和通道非常复杂。多种通道同工型有助于伤害感受性感觉神经元中的宏观电流。这些不同的同工型在动力学和药理学方面存在显著差异。此外，钠离子电流的复杂性还受到一系列相互作用的蛋白质的增强，这些蛋白质可以显著改变电压门控钠离子通道的性质。复发性钠离子电流是一种可以增强失活和神经元放电恢复的非典型电流，它在感觉神经元过度兴奋和疼痛感觉中被认为具有潜在的重要作用。本文讨论了在伤害感受性感觉神经元中已鉴定出的异常钠离子通道和电流，描述了已知的这些神经元中复杂钠离子电流的分子决定因素。最后，我们概述了针对伤害感受性神经元电压门控钠离子电流的治疗策略。
