Modeling Approaches for Paclitaxel-Induced Peripheral Neuropathy in Rats and Mice

Abstract

Peripheral neuropathy is one of the most common adverse effects of chemotherapeutic drugs, including taxanes. Paclitaxel is a cytostatic antitumor drug whose mechanism of action is associated with the stabilization of microtubule polymerization, causing mitosis arrest followed by apoptotic cell death. The need to develop new approaches to preventing and alleviating drug-induced peripheral neuropathy makes the study of its modeling features in laboratory animal particularly relevant. This work analyzes modern approaches to the modeling of paclitaxel-induced neuropathy and identifies factors influencing the severity of pain sensitivity in animals. A review of experimental articles retrieved from the PubMed and Google Scholar databases showed that, at present, repeated intraperitoneal injections of the cytostatic at doses from 2 to 8 mg/kg, simulating chemotherapy in humans, are most often used to model paclitaxel-induced neuropathy. When assessing sex and age differences in the manifestation of symptoms of paclitaxel-induced neuropathy, they were found to be more pronounced in mice compared to rats, being more pronounced in young animals. Thus, when modeling paclitaxel-induced neuropathy in rats and mice, it is necessary to take into account the species, strain, sex and age of animals, the dose and dosing schedule of the cytostatic. Prevention of axonal degeneration caused by chemotherapy may be a new promising direction of research for drug development.