Papers of the Week

Cyclovirobuxine D (CVB-D), the main active constituent of traditional Chinese medicine , was developed as a safe and effective cardiovascular drug in China. has also been used to relieve various pain symptoms for centuries. In this study, we examined and uncovered strong and persistent analgesic effects of cyclovirobuxine D against several mouse models of pain, including carrageenan- and CFA-induced inflammatory pain and paclitaxel-mediated neuropathic hypersensitivity. Cyclovirobuxine D shows comparable analgesic effects by intraplantar or intraperitoneal administration. Cyclovirobuxine D potently inhibits voltage-gated Ca2.2 and Ca3.2 channels but has negligible effects on a diverse group of nociceptive ion channels distributed in primary afferent neurons, including Na1.7, Na1.8, TRPV1, TPRA1, TRPM8, ASIC3, PX and PX. Moreover, inhibition of Ca3.2, rather than Ca2.2, plays a dominant role in attenuating the excitability of isolated dorsal root ganglion neurons and pain relieving effects of cyclovirobuxine D. Our work reveals that a currently in-use cardiovascular drug has strong analgesic effects mainly blockade of Ca3.2 and provides a compelling rationale and foundation for conducting clinical studies to repurpose cyclovirobuxine D in pain management.