title: Chemotherapy-induced peripheral neurotoxicity in immune-deficient mice: new useful ready-to-use animal models.
abstract: Cisplatin, paclitaxel and bortezomib are effective chemotherapy drugs in cancer treatment. However, they share severe peripheral neurotoxicity (PN) as one of their major dose-limiting side effects, often impairing cancer patients' quality of life and sometimes being permanent. Even if preclinical oncology is largely based on the use of immune-deficient mice, rodent models used to study the chemotherapy-induced PN are available only in immune-competent animals. In this study we characterized for the first time the PN induced by these chemotherapies through neurophysiological, behavioral, morphological and morphometric studies in athymic nude mice, a commonly employed strain in the preclinical oncology. The animals, divided into four groups, were chronically treated with cisplatin, paclitaxel or bortezomib once or twice a week for 4 or 6 weeks or were left untreated. These schedules were tolerated, neurotoxic and in the range of antineoplastic effectiveness. Despite similarities, differences in the features of PN were evident if compared with immune-competent models under comparable regimens of treatment. The results of this study may provide a basis for future combined analysis of antineoplastic and neurotoxic effects of chemotherapy in the same animals.
authors.affiliation: Experimental Neurology Unit and Center for Neuroscience of Milan, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, MB, Italy; Young Against Pain (YAP) Italian Group, Italy. Electronic address: valentina.carozzi1@unimib.it.
authors.forename: Valentina Alda
authors.initials: VA
authors.lastname: Carozzi
authors.affiliation: Experimental Neurology Unit and Center for Neuroscience of Milan, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, MB, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Chiorazzi
authors.affiliation: Experimental Neurology Unit and Center for Neuroscience of Milan, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, MB, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Canta
authors.affiliation: Experimental Neurology Unit and Center for Neuroscience of Milan, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, MB, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Meregalli
authors.affiliation: Experimental Neurology Unit and Center for Neuroscience of Milan, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, MB, Italy.
authors.forename: Norberto
authors.initials: N
authors.lastname: Oggioni
authors.affiliation: Experimental Neurology Unit and Center for Neuroscience of Milan, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, MB, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Cavaletti
authors.affiliation: Experimental Neurology Unit and Center for Neuroscience of Milan, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, MB, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Marmiroli
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000172:deficiency* / Q000235:genetics; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D006930:Hyperalgesia / Q000209:etiology; D051379:Mice; D008819:Mice, Nude; D009431:Neural Conduction / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000209:etiology* / Q000473:pathology; D059225:Nociception / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D012584:Sciatic Nerve / Q000473:pathology; D012684:Sensory Thresholds / Q000187:drug effects; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D051858:Forkhead Transcription Factors; C090140:Whn protein
keywords: Athymic mice; Bortezomib; Cisplatin; Paclitaxel; Painful peripheral neuropathy