title: Involvement of oxidative stress in increased peripheral nerve firing during spontaneous dysesthesia in a mouse model of ischemia-reperfusion.
abstract: Transient ischemia-reperfusion in the hand and foot elicits spontaneous dysesthesia. However, the mechanisms by which this occurs are not completely understood. The objectives of this study were to examine peripheral neural activity related to spontaneous dysesthesia in a mouse model of hind-paw transient ischemic-reperfusion and to investigate the involvement of oxidative stress in this neural activity. The femoral artery and vein were interrupted for 10min using tourniquet pressure, before the tourniquet was removed to allow reperfusion of the hind paw. Neural activity in the saphenous nerve was recorded during both ischemia and reperfusion. In both the ischemic phase and the reperfusion phase, the frequency of saphenous nerve firing was significantly increased compared to baseline. The antioxidant agent N-acetyl-l-cysteine inhibited significantly the firing of the saphenous nerve in both the maximum and minimum activity periods during ischemia, and in the maximum activity state after reperfusion percentage inhibition being approximately 68%, 60%, and 58%, respectively. In the reperfusion phase, the production of 4-hydroxy-2-noneal, a major product of endogenous lipid peroxidation, was significantly increased in the plantar skin, and this was inhibited by N-acetyl-l-cysteine. In the ischemic phase, a similar trend was observed. These results suggest that an increase in peripheral nerve activity related to oxidative stress may be involved in the spontaneous dysesthesia induced by transient ischemia-reperfusion.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; Research Unit/Neuroscience Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kagaya
authors.affiliation: Research Unit/Neuroscience Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Research Unit/Neuroscience Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Kino
authors.affiliation: Advanced Drug Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: andoht@pha.u-toyama.ac.jp.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
mesh_terms: D000200:Action Potentials; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010292:Paresthesia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000503:physiopathology*; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D012867:Skin / Q000098:blood supply / Q000378:metabolism
chemical_list: D000447:Aldehydes; C027576:4-hydroxy-2-nonenal
keywords: 4-Hydroxy-2-noneal; Dysesthesia; Hydrogen peroxide; Ischemia-reperfusion; Oxidative stress; Saphenous nerve