Rodent Models of Chemotherapy-Induced Peripheral Neuropathy

Peripheral neuropathy is a common and dose-limiting side effect of many chemotherapeutic drugs. These include platinum compounds, taxanes, vinca alkaloids, proteasome inhibitors, and others such as thalidomide and suramin. Although many rodent models have been developed using either mice or rats, there is limited consistency in the dose or mode of delivery of the drug; the sex, age, and genetic background of the animal used in the study; and the outcome measures used in evaluation of the peripheral neuropathy. Behavioral assays are commonly used to evaluate evoked sensory responses but are unlikely to be a good representation of the spontaneous sensory paresthesias that the patients experience. Electrophysiologic tests evaluate the integrity of large myelinated populations and are useful in drugs that cause either demyelination or degeneration of large myelinated axons but are insensitive to degeneration of unmyelinated axons in early stages of neuropathy. Histopathologic tools offer an unbiased way to evaluate the degree of axonal degeneration or changes in neuronal cell body but are often time consuming and require processing of the tissue after the study is completed. Nevertheless, use of drug doses and mode of delivery that are relevant to the clinical protocols and use of outcome measures that are both sensitive and objective in evaluation of the length-dependent distal axonal degeneration seen in most chemotherapy-induced peripheral neuropathies may improve the translational utility of these rodent models.