Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, Japan.
Clin Neurophysiol. 2010 May;121(5):719-24. doi: 10.1016/j.clinph.2009.12.034. Epub 2010 Jan 22.
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.
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.
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).
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.
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.
研究神经病理性疼痛患者轴突持续钠离子电流的变化，以及利多卡因类似物美西律对轴突兴奋性的影响。
采用潜伏叠加技术，在 17 例神经病理性疼痛/感觉异常患者接受美西律治疗前后，估计浅感觉桡神经轴突的节段性持续钠离子电流。给予短暂的超极化条件电流，以条件-测试间隔为 0.2ms 的阈值变化作为持续钠离子电流大小的指标。
潜伏叠加时的 0.2ms 阈值变化在神经病理性疼痛患者中明显大于正常对照组（p<0.001）。美西律治疗后，临床疼痛评分降低（p<0.001），同时 0.2ms 的阈值变化也降低（p<0.001）。
在神经病变患者中，大感觉纤维的节段性持续钠离子电流增加，美西律可以抑制异常电流。美西律治疗后疼痛减轻，提示小纤维介导的神经病理性疼痛中的过度钠离子电流也可能被抑制。
潜伏叠加可用于大感觉纤维节段性钠离子电流的间接体内监测，未来在小纤维中应用该方法将为神经病理性疼痛的外周机制提供新的见解。
