Experimental assessment of the temporal dynamics of motor impairments in neuropathy induced by paclitaxel, cisplatin, and their concomitant administration

Background. Chemotherapy-induced peripheral neuropathy is a common complication of anticancer therapy with taxane- and platinum-based agents and is accompanied by persistent motor impairments that significantly limit the body’s functional capacity and reduce patients’ quality of life. Despite the clinical significance of motor deficits, their temporal dynamics and severity under concurrent administration of paclitaxel and cisplatin remain insufficiently studied. Purpose – to compare the temporal dynamics and severity of motor impairments in rats with chemotherapy-induced peripheral neuropathy following administration of paclitaxel, cisplatin, and their concurrent use over a 120-day observation period. Materials and Methods. The study was conducted on adult male inbred white rats, divided into four groups: intact control, paclitaxel (cumulative dose 8 mg/kg, intraperitoneally), cisplatin (cumulative dose 16 mg/kg, intraperitoneally), and a combination group. In the combination group, animals received cisplatin at 2 mg/kg and paclitaxel at 5 mg/kg once weekly for six weeks, providing a cumulative dose of 12 mg/kg for cisplatin and 30 mg/kg for paclitaxel. This regimen corresponded to standard clinical protocols of paclitaxel (175 mg/m²) and cisplatin (75 mg/m²) when adjusted for body surface area. Motor activity and coordination were assessed on days 1, 7, 14, 28, 60, 90, and 120 using the Open Field and Rotarod tests with a patented device for evaluating coordination and muscle endurance. Results. Chemotherapy-treated animals demonstrated persistent reductions in overall motor activity and coordination compared to the intact control group. Motor deficits developed from day 7 with paclitaxel, whereas cisplatin-induced impairments appeared as early as day 1. The most pronounced and long-lasting changes were observed under concurrent administration of paclitaxel and cisplatin, persisting throughout the 120-day observation period. Conclusions. Paclitaxel and cisplatin induce long-term motor deficits in an experimental model of chemotherapy-induced peripheral neuropathy, with combined administration resulting in the most severe impairments of coordination and activity. Behavioral tests such as Open Field and Rotarod provide informative tools for assessing the temporal dynamics and severity of motor dysfunction in neurotoxicity models.