Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy.
Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy.
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DOI：
10.1186/1744-8069-8-17
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发表时间：
2012-03-22
期刊：
影响因子：
3.3
通讯作者：
Fink DJ
中科院分区：
文献类型：
--
作者：
Chattopadhyay M;Zhou Z;Hao S;Mata M;Fink DJ
疼痛性神经病变是糖尿病的常见并发症。先前的研究已经确定了链脲佐菌素（STZ）诱导的糖尿病大鼠背根神经节（DRG）中电压门控钠通道亚型NaV1.7和NaV1.3蛋白的量显著增加。我们发现，基因转移介导的释放抑制性神经递质脑啡肽或γ氨基丁酸（GABA）从糖尿病动物的DRG神经元减少疼痛相关的行为与减少在体内的DRG中的NaV1.7蛋白水平一致。为了进一步评估DRG中NaVα亚基水平在糖尿病神经病变疼痛发病机制中的作用，我们构建了一种基于非复制型单纯疱疹病毒（HSV）的表达针对NaVα亚基的microRNA（miRNA）的载体。将表达miRNA的HSV载体皮下接种到糖尿病大鼠的足中，使DRG神经元中的NaVα亚基水平降低，与冷异常性疼痛、热痛觉过敏和机械痛觉过敏的降低一致。这些数据支持DRG中NaVα蛋白增加在糖尿病神经病变疼痛发病机制中的作用，并为开发可用于治疗糖尿病神经病变患者顽固性疼痛的新型疗法提供了原理验证。
Painful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms NaV1.7 and NaV1.3 protein in the dorsal root ganglia (DRG) of rats with streptozotocin (STZ)-induced diabetes. We found that gene transfer-mediated release of the inhibitory neurotransmitters enkephalin or gamma amino butyric acid (GABA) from DRG neurons in diabetic animals reduced pain-related behaviors coincident with a reduction in NaV1.7 protein levels in DRG in vivo. To further evaluate the role of NaVα subunit levels in DRG in the pathogenesis of pain in diabetic neuropathy, we constructed a non-replicating herpes simplex virus (HSV)-based vector expressing a microRNA (miRNA) against NaVα subunits. Subcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in NaVα subunit levels in DRG neurons, coincident with a reduction in cold allodynia, thermal hyperalgesia and mechanical hyperalgesia. These data support the role of increased NaVα protein in DRG in the pathogenesis of pain in diabetic neuropathy, and provide a proof-of-principle demonstration for the development of a novel therapy that could be used to treat intractable pain in patients with diabetic neuropathy.
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DOI：
10.1016/j.bbrc.2005.11.057
发表时间：
2006-01-13
影响因子：
3.1
作者：
Hong, SS;Wiley, JW
通讯作者：
Wiley, JW
影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.ejpain.2011.03.007
发表时间：
2011-10
期刊：
European journal of pain (London, England)
影响因子：
--
作者：
Chattopadhyay M;Mata M;Fink DJ
通讯作者：
Fink DJ
影响因子：
4.8
作者：
Hong, SS;Morrow, TJ;Wiley, JW
通讯作者：
Wiley, JW
影响因子：
5.3
作者：
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通讯作者：
Waxman, Stephen G.