Absence of an association between axotomy-induced changes in sodium currents and excitability in DRG neurons from the adult rat
Absence of an association between axotomy-induced changes in sodium currents and excitability in DRG neurons from the adult rat
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DOI：
10.1016/j.pain.2004.02.024
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发表时间：
2004-06-01
期刊：
影响因子：
7.4
通讯作者：
Gold, MS
中科院分区：
文献类型：
--
作者：
Flake, NM;Lancaster, E;Gold, MS
一般认为，神经损伤导致神经元过度兴奋，这部分反映了Na+电流的变化。然而，Na+电流变化的性质和Na+电流改变与兴奋性增加之间的关联存在相互矛盾的数据。相互矛盾的数据的一个潜在来源是，受伤的和幸免的神经元可能会对神经损伤作出不同的反应;这些神经元亚群在以前的研究中没有区分神经损伤的轴突切断模型（坐骨神经完全横断）。本研究旨在确定轴突切断后受损背根神经节神经元中Na+通道的变化与神经元兴奋性变化之间的关系。在轴突切断后10天和4周研究了用DiI注射到坐骨神经中标记的小（< 45 pF）神经元。轴突切断后10天，河豚毒素抗性（TTX-R）Na+电流（I-Na）降低，河豚毒素敏感性（TTX-S）INa增加，但兴奋性不变。轴突切断后4周，神经元变得过度兴奋，而TTX-R I-Na保持减少，TTX-S I-Na已恢复到对照水平。因此，轴突切断引起的Na+电流变化与轴突切断引起的兴奋性变化无关。轴突切断神经元的其他分析表明，伴随着其他离子电流的变化发生。这些结果表明，神经轴突切断后的神经元兴奋性是依赖于离子电流的变化的总和，和兴奋性的整体效果可能并不总是对应于预测的变化，在一个单一的电压门控离子通道类。(C)2004年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
It is generally believed that nerve injury results in neuronal hyperexcitability that reflects in part a change in Na+ currents. However, there are conflicting data on the nature of Na+ current changes and the association between alterations in Na+ currents and increases in excitability. One potential source of conflicting data is that injured and spared neurons may respond differently to nerve injury; these subpopulations of neurons have not been distinguished in previous studies with the axotomy model of nerve injury (complete transection of the sciatic nerve). The present study was performed to determine the relationship between changes in Na+ channels and changes in neuronal excitability in identified injured dorsal root ganglion neurons post-axotomy. Small (< 45 pF) neurons labeled with a DiI injection into the sciatic nerve were studied 10 days and 4 weeks post-axotomy. Ten days post-axotomy, tetrodotoxin-resistant (TTX-R) Na+ current (I-Na) was decreased and TTX-sensitive (TTX-S) INa was increased, however, excitability was unchanged. Four weeks post-axotomy, neurons had become hyperexcitable while TTX-R I-Na remained reduced and TTX-S I-Na had returned to control levels. Thus, axotomy-induced changes in Na+ currents were not correlated with an axotomy-induced change in excitability. Additional analysis of axotomized neurons suggested that concomitant changes in other ionic currents occurred. These results suggest that neuronal excitability following axotomy is dependent on the sum of changes in ionic currents, and the overall effect on excitability may not always correspond to that predicted by a change in a single class of voltage-gated ion channel. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.