TY - JOUR T1 - A Mouse Model of Peripheral Post-Ischemic Dysesthesia: Involvement of Reperfusion-Induced Oxidative Stress and TRPA1 Channel JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.114.217570 SP - jpet.114.217570 AU - Atsushi Sasaki AU - Shizuka Mizoguchi AU - Kenta Kagaya AU - Mai Shiro AU - Akiho Sakai AU - Tsugunobu Andoh AU - Yurika Kino AU - Hiroyuki Taniguchi AU - Yukako Saito AU - Hiroki Takahata AU - Yasushi Kuraishi Y1 - 2014/01/01 UR - http://jpet.aspetjournals.org/content/early/2014/09/16/jpet.114.217570.abstract N2 - We behaviorally examined peripheral post-ischemic dysesthesia in mice and investigated the underlying molecular mechanism with a focus on oxidative stress. Hind-paw ischemia was induced by tight compression of the ankle with a rubber band, and reperfusion was achieved by cutting the rubber tourniquet. We found that reperfusion after ischemia markedly provoked licking of the reperfused hind paw, which was significantly inhibited by systemic administration of the antioxidant N-acetyl-L-cysteine and the TRPA1 channel blocker HC-030031. Post-ischemic licking was also significantly inhibited by an intraplantar injection of another antioxidant phenyl-N-tert-butylnitrone. The TRPV1 channel blocker N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide did not inhibit post-ischemic licking. An intraplantar injection of hydrogen peroxide elicited hind-paw licking, which was inhibited by N-acetyl-L-cysteine, phenyl-N-tert-butylnitrone, and HC-030031. Post-ischemic licking was not affected by chemical depletion of sensory C-fibers, but it was inhibited by morphine, which has been shown to inhibit the C- and Aδ-fiber-evoked responses of dorsal horn neurons. Interestingly, post-ischemic licking was not inhibited by gabapentin and pregabalin, which have been shown to inhibit the C-fiber- but not Aδ-fiber-evoked response. The present results suggest that ischemia-reperfusion induces oxidative stress, which activates TRPA1 channels to provoke post-ischemic licking. This behavior is suggested to be mediated by myelinated (probably Aδ-type) afferent fibers. Oxidative stress and TRPA1 channels may be potential targets to treat peripheral ischemia-associated dysesthesia. ER -