A novel human foamy virus mediated gene transfer of GAD67 reduces neuropathic pain following spinal cord injury

• Published in: Neuroscience letters 2008-02, Vol.432 (1), p.13-18
• Main Authors: Liu, Wanhong, Liu, Zhongchun, Liu, Li, Xiao, Zheman, Cao, Xiongbin, Cao, Zhijian, Xue, Lu, Miao, Lixia, He, Xiaohua, Li, Wenxin
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; GAD; gamma-Aminobutyric Acid - physiology; Ganglia, Spinal - physiology; Gene therapy; Gene Transfer Techniques; Genetic Therapy - methods; Glutamate Decarboxylase - genetics; HFV; Hyperalgesia - etiology; Hyperalgesia - therapy; Injections, Subcutaneous; Male; Neuralgia - etiology; Neuralgia - therapy; Neuropathic pain; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries - complications; Spumavirus - genetics; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2007.11.054

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.