The natural product argentatin C attenuates postoperative pain via
inhibition of voltage-gated sodium and T-type voltage-gated calcium
Background and purpose: Postoperative pain occurs in as many as 70% of
the over 230 million surgeries performed annually worldwide.
Postoperative pain management still relies on opioids despite their
negative consequences, resulting in a public health crisis. Therefore,
it is of utmost importance to develop alternative therapies to treat
chronic pain. Natural products derived from medicinal plants are
potential sources of novel and are potential sources biologically active
compounds for development of novel analgesics safe analgesics.
Experimental approach: Hence, in this study, we screened a library of
natural products to identify small molecules that target the activity of
voltage-gated sodium and calcium channels due to their important roles
in nociceptive sensory processing. Key Results: We found that fractions
derived from the Native American medicinal plant, Parthenium incanum,
inhibited depolarization-evoked calcium influx in rat dorsal root
ganglion (DRG) neurons. Further separation of these fractions yielded a
cycloartane-type triterpene identified as argentatin C which blocked the
activity of both voltage-gated sodium and calcium channels in calcium
imaging assays. Docking analysis predicted that argentatin C may bind to
NaV1.7-1.9 and CaV3.1-3.3 channels. Furthermore, voltage and current
clamp electrophysiology experiments showed that argentatin C decreased
Na+ and T-type Ca2+ currents as well as excitability in rat and macaque
DRG neurons. Consistent with these observations, argentatin C treatment
reversed mechanical allodynia in a mouse model of postsurgical pain.
Conclusions & Implications: The dual effect of argentatin C on
voltage-gated sodium and calcium channels supports its potential as a
novel treatment for painful conditions.