Utidelone induces mechanical and cold allodynia in mice via TRPA1 activation.

Abstract

OBJECTIVE: Utidelone (UTD1), a recently approved epothilones analog in China for metastatic breast cancer, is endorsed in combination with capecitabine for metastatic breast cancer patients who have encountered first-line therapy failures. Despite its clinically verified therapeutic efficacy, it is concurrently associated with peripheral neuropathic pain, particularly affecting extremities. However, the etiology of UTD1-induced peripheral neuropathic pain remains unclear. METHODS: The present investigation built a mouse pain model induced by UTD1, resulting in marked mechanical and cold allodynia. RESULTS: Examination of the dorsal root ganglia unveiled a notable upregulation of TRPA1, accompanied by noteworthy alterations in oxidative stress-related markers, including ATF4, SOD2, CAT, and Cyt-C. The TRPA1 antagonist HC-030031, resulted in the alleviation of mechanical and cold allodynia in the UTD1-induced pain model, as well as two antioxidants, including Mito-tempo and edaravone. INTERPRETATION: The present study will provide new strategies for pain relieving induced by UTD1.