Puerarin Relieves Paclitaxel-Induced Neuropathic Pain: The Role of Nav1.8 β1 Subunit of Sensory Neurons
Puerarin Relieves Paclitaxel-Induced Neuropathic Pain: The Role of Nav1.8 β1 Subunit of Sensory Neurons
复制标题
葛根素缓解紫杉醇引起的神经性疼痛：感觉神经元 Nav1.8 β1 亚基的作用
DOI：
10.3389/fphar.2018.01510
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发表时间：
2019-01
影响因子：
5.6
通讯作者：
Wei-An Zeng
中科院分区：
文献类型：
--
作者：
Xiao-Long Zhang;Xian-Ying Cao;Ren-Chun Lai;Man-Xiu Xie;Wei-An Zeng
目前，临床上尚无有效的治疗紫杉醇化疗所致神经病理性疼痛的方法。葛根素是从中草药葛根中提取的一种主要异黄酮类化合物，已用于治疗心血管疾病和脑损伤。在这里，我们发现葛根素呈剂量依赖性地减轻紫杉醇诱导的神经病理性疼痛。同时，葛根素可优先抑制紫杉醇诱导的神经病理性疼痛大鼠背根神经节神经元的兴奋性，并阻断其电压门控性钠通道。此外，葛根素是慢性痛大鼠背根神经节神经元河豚毒素抵抗(TTX-R)NAV通道的阻断剂，而不是河豚毒素敏感(TTX-S)NAV通道的阻断剂。此外，葛根素对神经病理性疼痛大鼠背根神经节神经元NAV1.8通道有较强的阻断作用，β1亚单位siRNA可取消这种选择性阻断作用。以上结果提示，葛根素可能优先阻断感觉神经元NAV1.8的β1亚单位，参与其抗紫杉醇诱导的神经病理性疼痛效应。
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 (Nav) 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) Nav channels than of tetrodotoxin-sensitive (TTX-S) Nav channels in chronic pain rats’ DRG neurons. In addition, puerarin had a stronger blocking effect on Nav1.8 channels in DRG neurons of neuropathic pain rats and β1 subunit siRNA can abolish this selective blocking effect on Nav1.8. Together, these results suggested that puerarin may preferentially block β1 subunit of Nav1.8 in sensory neurons contributed to its anti-paclitaxel induced neuropathic pain effect.
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DOI：
10.1523/jneurosci.23-32-10338.2003
发表时间：
2003-11
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
Nathaniel T. Blair;B. Bean
通讯作者：
Nathaniel T. Blair;B. Bean
影响因子：
5.5
作者：
ELLIOTT, AA;ELLIOTT, JR
通讯作者：
ELLIOTT, JR
影响因子：
2.9
作者：
Lyu, YS;Park, SK;Chung, JM
通讯作者：
Chung, JM
影响因子：
5.5
作者：
Rush, AM;Bräu, ME;Elliott, JR
通讯作者：
Elliott, JR
影响因子：
3.3
作者：
Blackburn-Munro, G;Fleetwood-Walker, SM
通讯作者：
Fleetwood-Walker, SM