HSV-mediated gene transfer of the glial cell-derived neurotrophic factor provides an antiallodynic effect on neuropathic pain.
Neuropathic pain is a difficult clinical problem that is often refractory to medical management. Glial-derived neurotrophic factor (GDNF) administered intrathecally has been shown to prevent or reduce pain in an animal model of neuropathic pain, but cannot be delivered in the required doses to treat human pain. We have previously demonstrated that peripheral subcutaneous inoculation of a replication-incompetent herpes simplex virus (HSV)-based vector can be used to transduce neurons of the dorsal root ganglion. To examine whether HSV-mediated expression of GDNF could be used to ameliorate neuropathic pain, we constructed a replication-incompetent HSV vector expressing GDNF. Subcutaneous inoculation of the vector 1 week after spinal nerve ligation resulted in a continuous antiallodynic effect that was maintained for 3-4 weeks. Reinoculation of the vector reestablished the antiallodynic effect with a magnitude that was at least equivalent to the initial effect. Vector-mediated GDNF expression blocked the nonnoxious touch-induced increase in c-fos expression in dorsal horn characteristic of the painful state. Gene transfer to produce a trophic factor offers a novel approach to the treatment of neuropathic pain that may be appropriate for human therapy.
Hao
Shuanglin
S
Department of Neurology, Pittsburgh, Pennsylvania 15213, USA.
Mata
Marina
M
Wolfe
Darren
D
Huang
Shaohua
S
Glorioso
Joseph C
JC
Fink
David J
DJ
D000818:Animals; D002908:Chronic Disease; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D018139:Simplexvirus
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016760:Proto-Oncogene Proteins c-fos