• S Lauren Kyte, Wisam Toma, Deniz Bagdas, Julie A Meade, Lesley D Schurman, Aron H Lichtman, Zhi-Jian Chen, Egidio Del Fabbro, Xianjun Fang, John W Bigbee, M Imad Damaj, and David A Gewirtz.
• Departments of Pharmacology and Toxicology (S.L.K., W.T., D.B., J.A.M., L.D.S., A.H.L., M.I.D., D.A.G.), Neurology (Z.-J.C.), Internal Medicine (E.D.F.), Biochemistry and Molecular Biology (X.F.), and Anatomy and Neurobiology (J.W.B.), and Massey Cancer Center (D.A.G.), Virginia Commonwealth University, Richmond, Virginia; and Experimental Animals Breeding and Research Center, Uludag University, Bursa, Turkey (D.B.) kytesl@vcu.edu tomawb@vcu.edu.
• J. Pharmacol. Exp. Ther. 2018 Jan 1; 364 (1): 110-119.

AbstractChemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN.Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

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