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 7days 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.

中文翻译：

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新型人类泡沫病毒介导的GAD67基因转移可减轻脊髓损伤后的神经性疼痛。

神经性疼痛是一种长期存在的临床问题，通常对医疗管理无能为力。具有治疗意义的特定基因的基因转移为神经性疼痛的治疗提供了一种新颖的方法。在这项研究中，我们测试了通过使用新型人类泡沫病毒（SCI）将谷氨酸脱羧酶（GAD）基因转移至背根神经节（DRG）细胞是否能够减轻低于损伤水平的中枢神经性疼痛。 HFV）载体以释放γ-氨基丁酸（GABA）。皮下接种复制缺陷型HFV载体，该载体在T13脊髓半切后表达GAD（载体rdvGAD67）7天，逆转了SCI引起的机械性异常性疼痛和热痛觉过敏。抗痛觉过敏作用持续6周，并通过重新接种得以恢复。我们还发现rdvGAD67的皮下接种可提高转导的DRG神经元的GAD产生和GABA释放。这些结果表明，HFV介导的基因转移至DRG可用于治疗SCI不完全后损伤水平以下的中枢神经性疼痛。