A novel human foamy virus mediated gene transfer of GAD67 reduces neuropathic pain following spinal cord injury.
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.
Liu
Wanhong
W
Hubei Province Key Laboratory of Allergy and Immunology, School of Medicine, Wuhan University, Wuhan 430071, PR China. liuwanhong@whu.edu.cn
Liu
Zhongchun
Z
Liu
Li
L
Xiao
Zheman
Z
Cao
Xiongbin
X
Cao
Zhijian
Z
Xue
Lu
L
Miao
Lixia
L
He
Xiaohua
X
Li
Wenxin
W
D000818:Animals; D001522:Behavior, Animal; D005727:Ganglia, Spinal / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005968:Glutamate Decarboxylase / Q000235:genetics*; D006930:Hyperalgesia / Q000209:etiology / Q000628:therapy; D007279:Injections, Subcutaneous; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*; D016092:Spumavirus / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1