Mexiletine suppresses nodal persistent sodium currents in sensory axons of patients with neuropathic pain |
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| Affiliation: | 1. Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, Japan;2. Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, Japan;3. Department of Neurology, Kyoto Prefectural Medical University, Kyoto, Japan;4. Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan;1. Hypnalgesics LLC, Brookline, MA, USA;2. Department of Psychology, National University of Singapore, Singapore;3. Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA;1. Department of Neurosurgery, St Vincent’s Hospital, 390 Victoria Street, Darlinghurst, NSW 2010, Australia;2. Department of Neurology, St Vincent’s Hospital, Darlinghurst, NSW, Australia;1. Rotman Research Institute at Baycrest Centre, University of Toronto, Toronto, Canada;2. Memory Research Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK;1. Department of Dermatology, Keio University School of Medicine, Tokyo, Japan;2. MSD Endowed Program for Allergy Research, Keio University School of Medicine, Tokyo, Japan;3. KOSÉ Endowed Program for Skin Care and Allergy Prevention, Keio University School of Medicine, Tokyo, Japan;4. Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan;5. Mitsubishi Electric Co., Power Device Industries, Kumamoto, Japan;6. St Luke’s International Hospital, Tokyo, Japan;7. Department of Dermatology, Tokyo Medical University, Tokyo, Japan;8. Department of Dermatology, School of Medicine, Toho University, Tokyo, Japan;9. Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan;10. Keio-Maruho Laboratory of Skin Barriology, Keio University School of Medicine, Tokyo, Japan;1. Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, United States;2. Neuromuscular Research Group at the Department of Orthopaedics, Otto-von-Guericke University, Magdeburg, Germany;3. Department of Applied Physics, University of Eastern Finland, Kuopio, Finland;4. Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland |
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| Abstract: | ObjectiveTo 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.MethodsThe 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.ResultsThreshold 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).ConclusionsIn 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.SignificanceLatent 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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