Electrophysiological Assessments in Peripheral Nerves and Spinal Cord in Rodent Models of Chemotherapy-Induced Painful Peripheral Neuropathy

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe side effect related to anticancer treatment, typically characterized by sensory symptoms including numbness, tingling in the distal extremities and neurophysiological impairments. CIPN is often painful, which is identified by adding a second “P” to the acronym. The incidence of CIPN is variable depending on the drug, pre-existing neuropathy, and clinical history, but generally increases with the cumulative dose and can also persist after treatment discontinuation. In the last 30 years, many rodent models of CIPN have been developed reproducing the clinical features of the pathology, useful to study the mechanisms of pathogenesis and test neuroprotective strategies. In this chapter, we will focus our attention on sensitive and reproducible methods to study the pathophysiology of chemotherapy-induced painful peripheral neuropathy (CIPPN), in animal models. In particular, we describe the techniques to record nerve conduction velocity and nerve excitability parameters in peripheral nerves and the electrical activity of wide dynamic range neurons of the dorsal horn of the spinal cord in mice, as parameters of evaluation of nerve function and painful neuronal sensitization, respectively. Our intent is to provide the reader with guidelines on how to prepare and manage the animals according to the 3Rs (Reduction, Refinement, and Replacement) principles, how to record neuronal activity and analyze resulting data and describe common technical problems and appropriate solutions. These protocols can also be useful to study peripheral nerve damage and pain of other origins, such as traumatic injury, inherited, or acquired neuropathies.