Polyneuropathy is a frequent and potentially severe side effect of clinical
tumor chemotherapy. The goal of this study was to characterize
paclitaxel-, cisplatin-,
vincristine- and
bortezomib-induced neuropathy in C57BL/6 mice with a comparative approach. The phenotype of the animals was evaluated at four time points with behavioral and electrophysiological tests, followed by histology. Treatment protocols used in this study were well tolerated and induced a sensory and predominantly axonal
polyneuropathy. Behavioral testing revealed normal motor coordination, whereas all mice receiving verum treatment developed
mechanical allodynia and distinct gait alterations. Electrophysiological evaluation showed a significant decrease of the caudal sensory nerve action potential amplitude for all
cytostatic agents and a moderate reduction of nerve conduction velocity for
cisplatin and
paclitaxel. This finding was confirmed by histological analysis of the sciatic nerve which showed predominantly axonal damage:
Paclitaxel and
vincristine affected mostly large myelinated fibers,
bortezomib small myelinated fibers and
cisplatin damaged all types of myelinated fibers to a similar degree. Neuropathic symptoms developed faster in
paclitaxel and
vincristine treated animals compared to
cisplatin and
bortezomib treatment. The animal models in this study can be used to elucidate pathomechanisms underlying
chemotherapy-induced
polyneuropathy and for the development of novel therapeutic and preventative strategies.