Preclinical research in chemotherapy-induced neuropathy: a systematic review in the context of pain treatment

Abstract

Chemotherapy-induced neuropathy (CIN) is a common side effect of cancer therapy and is frequently accompanied by pain. Paclitaxel, one of the most common cytostatic drugs, generates a well-described peripheral nerve injury, which may be experimen-tally mimicked in animal models. In line with our previous studies in paclitax-el-induced CIN models, we conducted a systematic review analyzing the structure and aims of animal studies using paclitaxel-induced CIN to analyze the design and structure of the studies in order to discuss their putative representativity and repro-ducibility and identify the mechanisms under investigation. We elected studies pub-lished in Pubmed and Scopus between 1 January 2018 and 3 December 2022. Ac-cording to a defined mesh of search, 70 original studies were screened. The mecha-nisms under study were mainly neuroinflammation at the periphery. Most studies used male Sprague-Dawley rats to induce paclitaxel-induced CIN at low doses of paclitaxel, and the analyses studies focused at 14-28 days of CIN. Mechanical noci-ceptive tests were preferred in the behavioral evaluation. The overall methodological quality was considered moderate, and the risk of bias was considered unclear. This review supports the perception that there are several flaws in the experimental design that frustrate the reproducibility of studies. In addition, clinical considerations should be considered when designing animal experiments, such as sex and age rep-resentativity. In this way the increasing number of experimental studies describing the mechanisms of CIN and repurposing drugs or developing new molecules for paclitaxel-induced CIN may increase their translation.