Sodium channels and mechanisms of neuropathic pain
Sodium channels and mechanisms of neuropathic pain
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DOI：
10.1016/j.jpain.2005.09.006
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发表时间：
2006-01-01
期刊：
影响因子：
4
通讯作者：
Devor, M
中科院分区：
文献类型：
--
作者：
Devor, M
Na+通道是具有能够选择性地通过Na+离子的电压门控中心孔的大型跨膜蛋白。它们是感觉神经元电兴奋性的关键决定因素，并通过控制传入脉冲放电在疼痛感觉中起关键作用。影响周围神经的损伤和疾病引起轴突病和脱髓鞘。这些神经病变的变化，反过来，触发膜重塑在受伤的传入，也许也在未受伤的邻居。重塑的一个主要后果是细胞兴奋性增加。这在很大程度上是由于亚型选择性异常的表达和贩运的Na+通道，也可能改变动力学特性的单一通道。过度兴奋的神经元表现出增强的膜共振、节律发生和异位尖峰。由此产生的过度放电构成了原发性神经性疼痛信号。此外，它触发并维持中枢敏感化。这放大了残余的传入输入，产生触觉异常性疼痛，它也放大了正在进行的异位，夸大了自发性疼痛。膜稳定Na+通道配体通过选择性降低受损传入神经的膜共振从而抑制异位兴奋性来抑制神经病理性疼痛。这些外周作用药物的临床有用性可能会通过减少其中枢副作用而增强。视角：神经病理性疼痛是神经损伤或疾病后在外周神经系统（PNS）和中枢神经系统（CNS）中发展的多种病理生理变化的复杂结果。所有或大部分CNS变化被认为是由于PNS的异常信号传导，特别是外周感觉神经元的电过度兴奋。由于过度兴奋与异常钠通道调节相关，因此该过程是治疗干预的主要目标。(c)2006年，美国疼痛协会。
Na+ channels are large transmembrane proteins with a voltage-gated central pore capable of selectively passing Na+ ions. They are critical determinants of the electrical excitability of sensory neurons and play a key role in pain sensation by controlling afferent impulse discharge. Injury and disease affecting peripheral nerves induces axonopathy and demyelination. These neuropathic changes, in turn, trigger membrane remodeling in injured afferents and perhaps also in uninjured neighbors. A major consequence of the remodeling is increased cellular excitability. This is due in large part to subtype-selective abnormalities in the expression and trafficking of Na+ channels and perhaps also to altered kinetic properties of unitary channels. Hyperexcitable neurons show enhanced membrane resonance, rhythmogenesis, and ectopic spiking. The resulting excess discharge constitutes a primary neuropathic pain signal. In addition, it triggers and maintains central sensitization. This amplifies residual afferent input, yielding tactile allodynia, and it also amplifies ongoing ectopia that exaggerates spontaneous pain. Membrane-stabilizing Na+ channel ligands suppress neuropathic pain by selectively reducing membrane resonance in injured afferents and hence ectopic hyperexcitability. The clinical usefulness of these peripherally acting drugs might be enhanced by reducing their central side effects. Perspective: Neuropathic pain is a complex outcome of multiple pathophysiological changes that develop in the peripheral nervous system (PNS) and the central nervous system (CNS) following nerve injury or disease. All or most of the CNS changes are thought to be due to abnormal signaling from the PNS, notably electrical hyperexcitability of peripheral sensory neurons. Because hyperexcitability is associated with abnormal sodium channel regulation, this process is a prime target for therapeutic intervention. (c) 2006 by the American Pain Society.