Methods for in vivo studies in rodents of chemotherapy induced peripheral neuropathy

Abstract

Peripheral neuropathy is one of the most common, dose limiting, and long-lasting disabling adverse events of chemotherapy treatment. Unfortunately, no treatment has proven efficacy to prevent this adverse effect in patients or improve the nerve regeneration, once it is established. Experimental models, particularly using rats and mice, are useful to investigate the mechanisms related to axonal or neuronal degeneration and target loss of function induced by neurotoxic drugs, as well as to test new strategies to prevent the development of neuropathy and to improve functional restitution. Therefore, objective and reliable methods should be applied for the assessment of function and innervation in adequately designed in vivo studies of CIPN, taking into account the impact of age, sex and species/strains features. This review gives an overview of the most useful methods to assess sensory, motor and autonomic functions, electrophysiological and morphological tests in rodent models of peripheral neuropathy, focused on CIPN. We include as well a proposal of protocols that may improve the quality and comparability of studies undertaken in different laboratories. It is recommended to apply more than one functional method for each type of function, and to perform parallel morphological studies in the same targets and models.

Keywords: Chemotherapy; Electrophysiology; Functional evaluation; Histology; Immunohistochemistry; Locomotion; Mouse; Neurotoxicity; Pain testing; Peripheral neuropathy; Rat.