Abstract
The population of patients with chemotherapy-induced neuropathy is increasing in parallel with the growing number of cancer survivors, creating an urgent need for effective treatments that address both the neuropathic symptoms and the accompanying depression. In this study, we established a mouse model of chronic oxaliplatin-induced neuropathy (OIPN) that closely mimics significant cold and mechanical allodynia, along with depression-like behaviors observed in patients, over a clinically relevant timeframe. We investigated the effects of fenofibrate on pain hypersensitivity and depression-like behaviors in the OIPN mouse model. Administration of fenofibrate significantly reduced mechanical allodynia in the Von Frey test and cold allodynia in the cold plate test among OIPN mice. Moreover, fenofibrate reduced depression-like behaviors in OIPN mice, as demonstrated by improved performance in the forced swimming test, sucrose preference test and tail suspension test. The analgesic and antidepressant-like effects observed with fenofibrate may be linked to its protective actions on oligodendrocyte progenitor cells (OPCs) in the medial prefrontal cortex (mPFC) of oxaliplatin-treated mice. These findings suggest that fenofibrate holds promise as a potential therapeutic agent for the prevention and treatment of OIPN, offering relief from both pain and comorbid depressive symptoms. Further clinical testing is warranted to confirm its efficacy and safety in this context.