EXPRESS: Utidelone induces mechanical and cold allodynia in mice via TRPA1 activation

Utidelone (UTD1), an epothilone analogue recently approved in China for treating metastatic breast Cancer, is recommended in conjunction with capecitabine for patients who have not responded to first-line therapies. Although its therapeutic effectiveness is clinically proven, it is also associated with peripheral neuropathic pain, predominantly in the extremities. The pathogenesis of UTD1-induced peripheral neuropathic pain, however, remains elusive. The current study established a mouse model of pain induced by UTD1, which led to significant mechanical and cold allodynia. Analysis of the dorsal root ganglia revealed a substantial upregulation of TRPA1, alongside significant changes in markers of oxidative stress, such as ATF4, SOD2, CAT, and Cyt-C. Administration of the TRPA1 antagonist HC-030031 significantly alleviated mechanical and cold allodynia in the UTD1-induced pain model, as did two Antioxidants, Mito-tempo and edaravone. This study proposes new approaches for mitigating pain caused by UTD1.

TRPA1; UTD1; dorsal root ganglion; mechanical and cold allodynia; oxidative stress.