Bulleyaconitine A preferably reduces tetrodotoxin-sensitive sodium current in uninjured dorsal root ganglion neurons of neuropathic rats probably via inhibition of protein kinase C
机构：[a]Pain Research Center, Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China,[b]Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China,临床科室其他部门手术麻醉科华南肿瘤学国家重点实验室中山大学肿瘤防治中心[c]Guangdong Provincial Key Laboratory of Brain Function and Disease, China,[d]Department of Pain Medicine, Beijing Tian Tan Hospital, Capital Medical University, Beijing, PR China首都医科大学附属天坛医院
Oral Bulleyaconitine A (BLA) is effective for treating neuropathic pain in human patients, but the underlying mechanism is poorly understood. Here, we tested whether BLA blocked voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons. Compelling evidence shows that voltage-gated sodium channels are upregulated in uninjured DRG neurons but downregulated in injured ones following peripheral nerve injury. We found that BLA preferably inhibited Na+ currents in uninjured DRG neurons in neuropathic rats. Compared to sham rats, IC50 values for resting and inactivated Na+ currents were 113 and 74 times lower in injured and uninjured neurons of L4-6 DRGs in spared nerve injury (SNI) rats (4.55 and 0.56 nM) and were 688 and 518 times lower in the uninjured L4 and L6 DRG neurons of L5 spinal nerve ligation (L5-SNL) rats. The use-dependent blockage of BLA on Na+ currents was more potent in neuropathic rats compared to sham rats. Bulleyaconitine A facilitated the inactivation of Na+ channels in each group. IC50 values for resting and inactivated tetrodotoxin-sensitive (TTX-S) channels were 1855 and 1843 times lower than those for TTX-resistant channels in the uninjured neurons of L5 spinal nerve ligation rats. The upregulation of protein kinase C was associated with the preferable effect of BLA on TTX-S Na+ channels in the uninjured DRG neurons. Local application of BLA onto L4-6 DRGs at 0.1 to 10 nM dose-dependently alleviated the mechanical allodynia and thermal hyperalgesia in L5 spinal nerve ligation model. Thus, preferable blockage of TTX-S Na+ channels in uninjured DRG neurons may contribute to BLA's antineuropathic pain effect.
基金：
National Natural Science Foundation of China [U1201223, 81471132]; Natural Science Foundation of Guangdong Province [2014A030313030]
语种：
外文
被引次数：
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PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区麻醉学2 区临床神经病学2 区神经科学
最新[2023]版：
大类|1 区医学
小类|1 区临床神经病学1 区神经科学2 区麻醉学
第一作者：
第一作者机构：[a]Pain Research Center, Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China,[b]Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China,
通讯作者：
通讯机构：[a]Pain Research Center, Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China,[b]Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China,[*1]Pain Research Center, Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510089, China.
推荐引用方式(GB/T 7714)：
Man-Xiu Xie,Rui-Ping Pang,Jie Yang,et al.Bulleyaconitine A preferably reduces tetrodotoxin-sensitive sodium current in uninjured dorsal root ganglion neurons of neuropathic rats probably via inhibition of protein kinase C[J].PAIN.2017,158(11):2169-2180.doi:10.1097/j.pain.0000000000001018.
APA：
Man-Xiu Xie,Rui-Ping Pang,Jie Yang,Kai-Feng Shen,Jing Xu...&Xian-Guo Liu.(2017).Bulleyaconitine A preferably reduces tetrodotoxin-sensitive sodium current in uninjured dorsal root ganglion neurons of neuropathic rats probably via inhibition of protein kinase C.PAIN,158,(11)
MLA：
Man-Xiu Xie,et al."Bulleyaconitine A preferably reduces tetrodotoxin-sensitive sodium current in uninjured dorsal root ganglion neurons of neuropathic rats probably via inhibition of protein kinase C".PAIN 158..11(2017):2169-2180
医学