Comparative effectiveness of antinociceptive gene therapies in animal models of diabetic neuropathic pain.
Comparative effectiveness of antinociceptive gene therapies in animal models of diabetic neuropathic pain.
复制标题
抗伤害基因疗法在糖尿病神经性疼痛动物模型中的比较效果。
DOI：
10.1038/gt.2012.90
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发表时间：
2013-07
期刊：
影响因子：
5.1
通讯作者：
Chiocca EA
中科院分区：
文献类型：
--
作者：
Wang Y;Nowicki MO;Wang X;Arnold WD;Fernandez SA;Mo X;Wechuk J;Krisky D;Goss J;Wolfe D;Popovich PG;Lawler S;Chiocca EA
周围神经性疼痛是糖尿病最常见且使人衰弱的并发症之一。在使用基于复制缺陷型单纯疱疹病毒 (HSV)1 的载体转移至背根神经节后，一些基因已被证明可有效减轻糖尿病动物模型中的神经性疼痛，但从未对其功效进行过比较分析。我们在链脲佐菌素诱导的糖尿病大鼠和小鼠模型中比较了四种不同的基于 HSV1 的载体，这些载体被设计为单独或组合产生两种阿片受体激动剂之一（脑啡肽或内吗啡）或两种谷氨酸脱羧酶亚型（GAD65 或 GAD67）之一。我们的结果表明，在大鼠中，单次皮下后爪接种表达GAD65或GAD67的载体可将糖尿病引起的机械性异常性疼痛降低到比每日注射加巴喷丁更大的程度。出现热痛觉过敏的糖尿病小鼠也对 GAD65 或内吗啡基因递送有反应。结果表明，GAD65 或 GAD67 载体在治疗糖尿病疼痛方面最有效。载体组合GAD67+内吗啡、GAD67+脑啡肽或内吗啡+脑啡肽也产生显着的镇痛作用，但该组合似乎并不优于单基因治疗。这些发现为用于治疗糖尿病周围神经病变的抗伤害基因疗法的临床开发提供了进一步的理由。
Peripheral neuropathic pain is one of the most common and debilitating complications of diabetes. Several genes have been shown to be effective in reducing neuropathic pain in animal models of diabetes after transfer to the dorsal root ganglion using replication-defective herpes simplex virus (HSV)1-based vectors, yet there has never been a comparative analysis of their efficacy. We compared four different HSV1-based vectors engineered to produce one of two opioid receptor agonists (enkephalin or endomorphin), or one of two isoforms of glutamic acid decarboxylase (GAD65 or GAD67), alone and in combination, in the streptozotocin-induced diabetic rat and mouse models. Our results indicate that a single subcutaneous hindpaw inoculation of vectors expressing GAD65 or GAD67 reduced diabetes-induced mechanical allodynia to a degree that was greater than daily injections of gabapentin in rats. Diabetic mice that developed thermal hyperalgesia also responded to GAD65 or endomorphin gene delivery. The results suggest that either GAD65 or GAD67 vectors are the most effective in the treatment of diabetic pain. The vector combinations, GAD67 + endomorphin, GAD67 + enkephalin or endomorphin + enkephalin also produced a significant antinociceptive effect but the combination did not appear to be superior to single gene treatment. These findings provide further justification for the clinical development of antinociceptive gene therapies for the treatment of diabetic peripheral neuropathies.
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HSV介导的白介素4在背根神经神经元中的表达减轻了神经性疼痛。
影响因子：
3.3
作者：
Hao S;Mata M;Glorioso JC;Fink DJ
通讯作者：
Fink DJ
影响因子：
4.7
作者：
Chen, Shao-Rui;Samoriski, Gary;Pan, Hui-Lin
通讯作者：
Pan, Hui-Lin
影响因子：
11.2
作者：
Hao, SG;Mata, M;Fink, DJ
通讯作者：
Fink, DJ
影响因子：
12.4
作者：
Liu, J;Wolfe, D;Fink, DJ
通讯作者：
Fink, DJ
影响因子：
6.1
作者：
Luft, D
通讯作者：
Luft, D