Zhang Xiao-Long, Cao Xian-Ying, Lai Ren-Chun, Xie Man-Xiu, Zeng Wei-An
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Anesthesiology, Sun Yat-sen University Cancer Center, Guangzhou, China.
College of Food Science and Technology, Hainan University, Haikou, China.
Front Pharmacol. 2019 Jan 7;9:1510. doi: 10.3389/fphar.2018.01510. eCollection 2018.
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 dose-dependently alleviated paclitaxel-induced neuropathic pain. At the same time, puerarin preferentially reduced the excitability and blocked the voltage-gated sodium (Na) 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 channels than of tetrodotoxin-sensitive (TTX-S) Na channels in chronic pain rats' DRG neurons. In addition, puerarin had a stronger blocking effect on Na1.8 channels in DRG neurons of neuropathic pain rats and β1 subunit siRNA can abolish this selective blocking effect on Na1.8. Together, these results suggested that puerarin may preferentially block β1 subunit of Na1.8 in sensory neurons contributed to its anti-paclitaxel induced neuropathic pain effect.
目前,对于患有化疗药物紫杉醇诱导的神经性疼痛的临床患者,尚无有效的治疗方法。葛根素是从中药葛根中提取的一种主要异黄酮,已被用于治疗心血管疾病和脑损伤。在此,我们发现葛根素能剂量依赖性地减轻紫杉醇诱导的神经性疼痛。同时,葛根素优先降低紫杉醇诱导的神经性疼痛大鼠背根神经节(DRG)神经元的兴奋性,并阻断其电压门控钠(Na)通道。此外,在慢性疼痛大鼠的DRG神经元中,葛根素对河豚毒素抗性(TTX-R)钠通道的阻断作用比对河豚毒素敏感性(TTX-S)钠通道更强。另外,葛根素对神经性疼痛大鼠DRG神经元中的Na1.8通道具有更强的阻断作用,而β1亚基小干扰RNA可消除这种对Na1.8的选择性阻断作用。总之,这些结果表明,葛根素可能优先阻断感觉神经元中Na1.8的β1亚基,这有助于其抗紫杉醇诱导的神经性疼痛作用。