Chemotherapy can come with some serious baggage, causing a variety of unpleasant side effects. One of the most challenging to treat is chemotherapy-induced peripheral neuropathy (CIPN). However, a study has discovered that rapamycin, an immunomodulatory drug, may hold the key to alleviating the neurotoxicity caused by cisplatin, a commonly used chemotherapy drug. In mice, rapamycin showed a significant reduction in nociceptive-like symptoms induced by cisplatin. Furthermore, it was found to reverse the increase in inflammatory mediators and neuronal apoptosis caused by cisplatin. By targeting specific proteins involved in the development and progression of neurotoxicity, rapamycin offered promising neuroprotection. This finding opens up avenues for further research into rapamycin as a potential treatment for chemotherapy-induced peripheral neuropathy in cancer patients.

Platinum-based chemotherapeutic treatment of cancer patients is associated with debilitating adverse effects. Several adverse effects have been well investigated, and can be managed satisfactorily, but chemotherapy-induced peripheral neuropathy (CIPN) remains poorly treated. Our primary aim in this study was to investigate the neuroprotective effect of the immunomodulatory drug rapamycin in the mitigation of cisplatin-induced neurotoxicity. Pain assays were performed in vivo to determine whether rapamycin would prevent or significantly decrease cisplatin-induced neurotoxicity in adult male Balb/c mice. Neuropathic pain induced by both chronic and acute exposure to cisplatin was measured by hot plate assay, cold plate assay, tail-flick test, and plantar test. Rapamycin co-treatment resulted in significant reduction in cisplatin-induced nociceptive-like symptoms. To understand the underlying mechanisms behind rapamycin-mediated neuroprotection, we investigated its effect on certain inflammatory mediators implicated in the propagation of chemotherapy-induced neurotoxicity. Interestingly, cisplatin was found to significantly increase peripheral IL-17A expression and CD8- T cells, which were remarkably reversed by the pre-treatment of mice with rapamycin. In addition, rapamycin reduced the cisplatin-induced neuronal apoptosis marked by decreased neuronal caspase-3 activity. The rapamycin neuroprotective effect was also associated with reversal of the changes in protein expression of p21Cip1, p53, and PUMA. Collectively, rapamycin alleviated some features of cisplatin-induced neurotoxicity in mice and can be further investigated for the treatment of cisplatin-induced peripheral neuropathy.

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