Kyte, S. LaurenToma, WisamMeade, Julie A.Schurman, Lesley D.Lichtman, Aron H.Chen, Zhi-JianDel Fabbro, EgidioFang, XianjunBigbee, John W.Damaj, M. ImadGewirtz, David A.2024-02-292024-02-292018-01-01Kyte, 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), 110-119.0022-35651521-0103jpet.aspetjournals.org/content/364/1/110https://hdl.handle.net/11452/40056Chemotherapy-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.eninfo:eu-repo/semantics/closedAccessPharmacology & pharmacyInduced peripheral neuropathyLung-cancer cellsBreast-cancerAcetylcholine-receptorsAccelerated senescencePostoperative painTumor-cellsIn-vıtroGrowthMiceAnimalsAntineoplastic agents, phytogenicBridged-ring compoundsCarcinoma, non-small-cell lungDisease models, animalHyperalgesiaLung neoplasmsMaleMiceMice, inbred C57BLNicotinePaclitaxelPeripheral nervous system diseasesReceptors, cholinergicTaxoidsArticle0004227085000122-s2.0-85039561554110119364129042416https://doi.org/10.1124/jpet.117.243972Pharmacology & pharmacyNicotinic Receptors; Nicotine Tartrate; BungarotoxinsMecamylamineMethyllycaconitineNicotinePaclitaxelAntineoplastic agentBridged compoundCholinergic receptorNicotinePaclitaxelTaxaneTaxoidA-549 cell lineAcute drug administrationAdultAllodyniaAnimal cellAnimal experimentAnimal modelAnimal tissueAntinociceptionApoptosisArticleC57BL 6 mouseCancer inhibitionCell densityCell proliferationCell viabilityChemotherapy-induced peripheral neuropathyChronic drug administrationControlled studyDose responseDrug cytotoxicityDrug effectDrug efficacyHumanHuman cellLung tumorMaleMouseNCI-H460 cell lineNeuroprotectionNonhumanPriority journalTreatment durationAnimalC57BL mouseChemically inducedDisease modelHyperalgesiaLung tumorMetabolismNon small cell lung cancerPeripheral neuropathy