Puerarin Relieves Paclitaxel-Induced Neuropathic Pain: The Role of Nav1.8 β1 Subunit of Sensory Neurons

Abstract

Currently there is no effective treatment available for clinical patients suffering from neuropathic pain induced by chemotherapy paclitaxel. Puerarin is a major isoflavonoid extracted from the Chinese medical herb kudzu root, which has been used for treatment of cardiovascular disorders and brain injury. Here, we found that puerarin dosedependently alleviated paclitaxel-induced neuropathic pain. At the same time, puerarin preferentially reduced the excitability and blocked the voltage-gated sodium (Na v ) channels of dorsal root ganglion (DRG) neurons from paclitaxel-induced neuropathic pain rats. Furthermore, puerarin was a more potent blocker of tetrodotoxin-resistant (TTX-R) Na v channels than of tetrodotoxin-sensitive (TTX-S) Na v channels in chronic pain rats' DRG neurons. In addition, puerarin had a stronger blocking effect on Na v 1.8 channels in DRG neurons of neuropathic pain rats and 1 subunit siRNA can abolish this selective blocking effect on Na v 1.8. Together, these results suggested that puerarin may preferentially block 1 subunit of Na v 1.8 in sensory neurons contributed to its anti-paclitaxel induced neuropathic pain effect.