Mexiletine suppresses nodal persistent sodium currents in sensory axons of patients with neuropathic pain
Mexiletine suppresses nodal persistent sodium currents in sensory axons of patients with neuropathic pain
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DOI：
10.1016/j.clinph.2009.12.034
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发表时间：
2010-05-01
影响因子：
4.7
通讯作者：
Kuwabara, Satoshi
中科院分区：
文献类型：
--
作者：
Isose, Sagiri;Misawa, Sonoko;Kuwabara, Satoshi
目的：探讨神经病理性疼痛患者轴突持续Na(+)电流的变化及利多卡因类似物美西律对轴突兴奋性的影响。方法：采用潜伏期相加技术，对17例神经病理性疼痛/感觉异常患者治疗前后的神经根浅层感觉轴突持续Na(+)电流进行检测。结果：神经病患者在潜伏期0.2ms时的阈值变化大于正常对照组(p<；0.001)。美西律治疗后临床疼痛评分降低(p<；0.001)，0.2ms时阈值改变降低(p<；0.001)。结论：神经病患者大感觉神经纤维上持续Na(+)电流增加，这种异常电流可被美西律抑制。美西律治疗后的疼痛减轻增加了这样一种可能性，即介导神经病理性疼痛的小纤维上过多的Na(+)电流也被抑制。意义：潜伏期添加可用于间接体内监测大感觉神经纤维上的结节Na(+)电流，未来在小纤维上使用这种方法的研究将为神经病理性疼痛的外周机制提供新的见解。(C)2010年国际临床神经生理学联合会。爱思唯尔爱尔兰有限公司出版。版权所有。
Objective: To investigate changes in axonal persistent Na(+) currents in patients with neuropathic pain and the effects of mexiletine, an analogue of lidocaine, on axonal excitability properties.Methods: The technique of latent addition was used to estimate nodal persistent Na(+) currents in superficial radial sensory axons of 17 patients with neuropathic pain/paresthesias before and after mexiletine treatment. Brief hyperpolarizing conditioning currents were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an indicator of the magnitude of persistent Na(+) currents.Results: Threshold changes at 0.2 ms in latent addition were greater in the neuropathic patients than in the normal controls (p < 0.001). After mexiletine treatment, there was a reduction in clinical pain scores (p < 0.001), associated with decreased threshold changes at 0.2 ms (p < 0.001).Conclusions: In patients with neuropathy, nodal persistent Na(+) currents in large sensory fibers increase, and the abnormal currents can be suppressed by mexiletine. Pain reduction after mexiletine treatment raises the possibility that excessive Na(+) currents are also suppressed in small fibers mediating neuropathic pain.Significance: Latent addition can be used for indirect in vivo monitoring of nodal Na(+) currents in large sensory fibers, and future studies using this approach in small fibers would provide new insights into the peripheral mechanism of neuropathic pain. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.