Chemotherapy-induced painful neuropathy: pain-like behaviours in rodent models and their response to commonly used analgesics.

Abstract

Chemotherapy-induced painful neuropathy (CIPN) is a major dose-limiting side-effect of several widely used chemotherapeutics. Rodent models of CIPN have been developed using a range of dosing regimens to reproduce pain-like behaviours akin to patient-reported symptoms. This review aims to connect recent evidence-based suggestions for clinical treatment to preclinical data. We will discuss CIPN models evoked by systemic administration of taxanes (paclitaxel and docetaxel), platinum-based agents (oxaliplatin and cisplatin), and the proteasome-inhibitor - bortezomib. We present an overview of dosing regimens to produce CIPN models and their phenotype of pain-like behaviours. In addition, we will discuss how potential, clinically available treatments affect pain-like behaviours in these rodent models, relating those effects to clinical trial data wherever possible. We have focussed on antidepressants, opioids, and gabapentinoids given their broad usage. The review outlines the latest description of the most-relevant rodent models of CIPN enabling comparison between chemotherapeutics, dosing regimen, rodent strain, and sex. Preclinical data support many of the recent suggestions for clinical management of established CIPN and provides evidence for potential treatments warranting clinical investigation. Continued research using rodent CIPN models will provide much needed understanding of the causal mechanisms of CIPN, leading to new treatments for this major clinical problem.