Novel human foamy virus mediated gene transfer of GAD67 reduces neuropathic pain following spinal cord injury
Novel human foamy virus mediated gene transfer of GAD67 reduces neuropathic pain following spinal cord injury
复制标题
新型人泡沫病毒介导的 GAD67 基因转移可减轻脊髓损伤后的神经性疼痛
DOI：
10.1016/j.neulet.2007.11.054
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发表时间：
2008-02-13
影响因子：
2.5
通讯作者：
Li, Wenxin
中科院分区：
文献类型：
--
作者：
Liu, Wanhong;Liu, Zhongchun;Li, Wenxin
神经病理性疼痛是一种长期的临床问题，往往是难治性的医疗管理。基因转移的特定基因的治疗效益提供了一种新的方法来治疗神经性疼痛。在这项研究中，我们测试了谷氨酸脱羧酶（GAD）基因转移到背根神经节（DRG）细胞是否会减轻脊髓损伤（SCI）后低于损伤水平的中枢神经病理性疼痛，通过使用一种新的人泡沫病毒（HFV）载体，以实现释放γ-氨基丁酸（GABA）。在T13脊髓半切后皮下接种表达GAD的复制缺陷型HFV载体（载体rdvGAD 67）7天，逆转了SCI诱发的机械性异常性疼痛和热痛觉过敏。抗异常性疼痛作用持续6周，并通过再接种重新建立。我们还发现，皮下接种rdvGAD 67导致GAD的产生和从转导的DRG神经元的紧张性GABA释放增强。这些结果表明，HFV介导的基因转移到背根节可以用于治疗不完全SCI后低于损伤水平的中枢神经病理性疼痛。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Neuropathic pain is a long-lasting clinical problem that is often refractory to medical management. Gene transfer of specific genes for therapeutic benefit offers a novel approach to the treatment of neuropathic pain. In this study, we tested whether the transfer of the glutamic acid decarboxylase (GAD) gene to dorsal root ganglion (DRG) cells would attenuate below-injury level central neuropathic pain after spinal cord injury (SCI) by using a novel human foamy virus (HFV) vector to achieve release of gamma-aminobutyric acid (GABA). Subcutaneous inoculation of a replication-defective HFV vector, which expresses GAD (vector rdvGAD67) for 7 days after T13 spinal cord hemisection, reversed mechanical allodynia and thermal hyperalgesia evoked by SCI. The antiallodynic effect lasted 6 weeks and was reestablished by reinoculation. We also found that subcutaneous inoculation of rdvGAD67 resulted in enhanced production of GAD and tonical GABA release from transduced DRG neurons. These results suggest that HFV-mediated gene transfer to DRG could be employed to treat below-injury level central neuropathic pain after incomplete SCI. (c) 2007 Elsevier Ireland Ltd. All rights reserved.