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  • Title: Mexiletine suppresses nodal persistent sodium currents in sensory axons of patients with neuropathic pain.
    Author: Isose S, Misawa S, Sakurai K, Kanai K, Shibuya K, Sekiguchi Y, Nasu S, Noto Y, Fujimaki Y, Yokote K, Kuwabara S.
    Journal: Clin Neurophysiol; 2010 May; 121(5):719-24. PubMed ID: 20097124.
    Abstract:
    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.
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