Gene therapy for trigeminal pain in mice.
Gene therapy for trigeminal pain in mice.
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DOI：
10.1038/gt.2014.14
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发表时间：
2014-04
期刊：
影响因子：
5.1
通讯作者：
Yeomans, D. C.
中科院分区：
文献类型：
--
作者：
Tzabazis, A. Z.;Klukinov, M.;Feliciano, D. P.;Wilson, S. P.;Yeomans, D. C.
本研究的目的是在小鼠三叉神经行为疼痛模型中测试编码脑磷脂的病毒载体的单次直接注射以诱导转基因的广泛表达和潜在镇痛作用的功效。在将编码人前脑啡肽原（SHPE）或lacZ报告基因（SHZ.1，对照病毒）的基于HSV-1的载体直接注射到小鼠三叉神经节中后，我们进行口面福尔马林试验并评估注射病毒载体后不同时间点的累积伤害性行为。我们观察到一个镇痛效果的伤害性行为，持续长达8周后，单次注射SHPE到三叉神经节。对照病毒注射的动物表现出与幼稚小鼠相似的伤害性行为。SHPE注射液的镇痛作用可被μ阿片受体拮抗剂纳洛酮逆转或减弱。注射SHPE的小鼠在皮下完全弗氏杆菌注射后，在发炎耳朵的热伤害性刺激后也显示出戒断乳的正常化，表明转基因的广泛表达。SHPE注射后三叉神经节定量免疫组化显示人前脑啡肽原表达。直接注射病毒载体被证明是有用的探索三叉神经系统的独特的病理生理学，也可能是一个有趣的除了疼痛治疗师的医疗设备。
The aim of this study was to test the efficacy of a single direct injection of viral vector encoding for encephalin to induce a widespread expression of the transgene and potential analgesic effect in trigeminal behavioral pain models in mice. After direct injection of HSV-1 based vectors encoding for human preproenkephalin (SHPE) or the lacZ reporter gene (SHZ.1, control virus) into the trigeminal ganglia in mice, we performed an orofacial formalin test and assessed the cumulative nociceptive behavior at different time points after injection of the viral vectors. We observed an analgesic effect on nociceptive behavior that lasted up to 8 weeks after a single injection of SHPE into the trigeminal ganglia. Control virus injected animals showed nociceptive behavior similar to naïve mice. The analgesic effect of SHPE injection was reversed/attenuated by subcutaneous naloxone injections, a μ-opioid receptor antagonist. SHPE injected mice also showed normalization in withdrawal latencies upon thermal noxious stimulation of inflamed ears after subdermal complete Freund’s adjuvans injection indicating widespread expression of the transgene. Quantitative immunohistochemistry of trigeminal ganglia showed expression of human preproenkephalin after SHPE injection. Direct injection of viral vectors proved to be useful for exploring the distinct pathophysiology of the trigeminal system and could also be an interesting addition to the pain therapists’ armamentarium.
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