Electrical stimulation with periodic alternating intervals stimulates neuronal cells to produce neurotrophins and cytokines through activation of mitogen-activated protein kinase pathways.
Peripheral neuropathy is a representative complication of dental surgery. Electrical therapy, based on electrical stimulation with periodic alternating intervals (ES-PAI), may promote nerve regeneration after peripheral nerve injury in a non-invasive manner, potentially providing an effective therapy for neuropathy. This study aimed to analyze the molecular mechanisms underlying the nerve recovery stimulated by ES-PAI. In brief, ES-PAI was applied to a neuronal cell line, Neuro2A, at various intensities using the pulse generator apparatus, FREUDE. Cell viability, neurotrophin mRNA expression, and cytokine production were examined using a tetrazolium-based assay, real-time RT-PCR, and ELISA, respectively. Mitogen-activated protein kinase (MAPK) signaling was assessed using flow cytometry. It was found that ES-PAI increased the viability of cells and elevated expression of nerve growth factor (NGF) and neurotrophin-3 (NT-3); ESPAI also augmented vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) expression, which was restored by addition of p38 inhibitors. Phosphorylation of p38 and extracellular signal-regulated kinase 1/2 (ERK-1/2) was augmented by ES-PAI. Hence, ES-PAI may ameliorate peripheral neuropathy by promoting neuronal cell proliferation and production of neurogenic factors by activating p38 and ERK-1/2 pathways.
Department of Dental Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.|Department of Immunology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.
Kenta
K
Yamamoto
Department of Dental Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.
Toshiro
T
Yamamoto
Department of Dental Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.|Department of Immunology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.
Kenichi
K
Honjo
Department of Dental Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.
Hiroaki
H
Ichioka
Department of Dental Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.
Fumishige
F
Oseko
Department of Immunology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.
Tsunao
T
Kishida
Department of Immunology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.
Osam
O
Mazda
Department of Dental Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan.
Narisato
N
Kanamura
D016207:Cytokines; D004558:Electric Stimulation; D006801:Humans; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D048051:p38 Mitogen-Activated Protein Kinases
D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
Neuro2a; electrical stimulation; mitogen-activated protein kinase; neurotrophins; peripheral neuropathy