Publication:
Nicotine prevents and reverses paclitaxel-induced mechanical allodynia in a mouse model of CIPN

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Date

2018-01-01

Authors

Bağdaş, Deniz

Authors

Kyte, S. Lauren
Toma, Wisam
Meade, Julie A.
Schurman, Lesley D.
Lichtman, Aron H.
Chen, Zhi-Jian
Del Fabbro, Egidio
Fang, Xianjun
Bigbee, John W.
Damaj, M. Imad

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Publisher

American Society for Pharmacology and Experimental Therapy

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Abstract

Chemotherapy-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 alpha 7 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.

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Keywords

Pharmacology & pharmacy, Induced peripheral neuropathy, Lung-cancer cells, Breast-cancer, Acetylcholine-receptors, Accelerated senescence, Postoperative pain, Tumor-cells, In-vıtro, Growth, Mice

Citation

Kyte, S. L. vd. (2018). ''Nicotine prevents and reverses paclitaxel-induced mechanical allodynia in a mouse model of CIPN''. Journal of Pharmacology and Experimental Therapeutics, 364(1), 110-119.

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