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Sodium channels and pain

机译：钠通道和疼痛

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Although it is well established that hyperaxcitability and /or increased baseline sensitivity of primary sensory neurons can lead to abnormal burst activity associated with pain, the underlying molecular mechanisms are not fully understood. Early studies demonstrated that, after in jury to their axons, neurons, can display changes in excitability, suggesting increased sodium channel expression, in fact, abnormal sodium channel accumulation has been observed at the tips of injured axons. We have used an ensemble of molecular, electrophysiological, and phaarmacological techniques to ask: what types of sodium channels underlie hyperexcitability of primary sensory neurons after injury? our studies demonstrate that multiple sodium channels, with distinct electrophysiological properties, are encoded by distinct mRNAs within small dorsal root ganglion (DRG) neurons, which include nociceptive cells. Moreover, several DRG neuron-specific sodium channels now have been cloned and sequenced. After injury to the axons of DRG neurons, there is a dramatic change in sodium channel expression in these cells, with down-regulation of some sodium channel genes and up-regulation of another, previously silent sodium channel gene. This plasticity in sodium channel gene expression is accompanied by electrophysiological changes that poise these cells to fire spontaneously or at inappropriate high frequencies. Changes in sodium channel gene expression also are observed in experimental models of inflammatory pain. Thus, sodium channel expression in DRG neurons is dynamic, changing significantly afte
机译：尽管已经充分认识到，初级感觉神经元的超兴奋性和/或增加的基线敏感性会导致与疼痛相关的异常爆发活动，但其潜在的分子机制尚未得到充分了解。早期研究表明，陪审团对神经元进行评审后，神经元可以表现出兴奋性变化，表明钠通道表达增加，实际上，在受伤的轴突尖端观察到异常的钠通道蓄积。我们已经使用了分子，电生理和药理学技术的综合方法来问：损伤后主要感觉神经元的过度兴奋是哪些类型的钠通道？我们的研究表明，具有不同电生理特性的多个钠通道由小的背根神经节（DRG）神经元（包括伤害性细胞）内的不同mRNA编码。此外，现在已经克隆并测序了几个DRG神经元特异性钠通道。在损伤DRG神经元的轴突后，这些细胞中的钠通道表达发生了显着变化，其中一些钠通道基因下调，而另一个以前沉默的钠通道基因上调。钠通道基因表达的这种可塑性伴随着电生理变化，使这些细胞自发地发射或以不适当的高频发射。在炎症性疼痛的实验模型中也观察到钠通道基因表达的变化。因此，DRG神经元中的钠通道表达是动态的，并在随后发生显着变化

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