Vector-mediated gene transfer to express inhibitory neurotransmitters in dorsal root ganglion reduces pain in a rodent model of lumbar radiculopathy.
METHODS
A prospective in vivo animal study.


OBJECTIVE
To examine the effect of the proenkephalin and glutamic acid decarboxylase (GAD)-expressing herpes simplex virus (HSV)-based vectors in a rodent model of lumbar radiculopathy.


BACKGROUND
We have previously shown that nonreplicating HSV-based vectors coding for proenkephalin or GAD can be used to transduce dorsal root ganglion (DRG) neurons in vivo to produce enkephalin or gamma-aminobutyric acid. HSV-mediated gene transfer of proenkephalin or GAD to DRG reduces pain-related behavior in rodent models of peripheral neuropathic pain.


METHODS
We created a model of lumbar radiculopathy by ligation of the dorsal and ventral lumbar roots proximal to the DRG. Three days later, we inoculated nonreplicating HSV-based vectors coding for proenkephalin or GAD subcutaneously in the foot.


RESULTS
Subcutaneous inoculation of either vector 3 days after ligation of the dorsal and ventral L5 lumbar roots resulted in a substantial and significant reduction in pain-related behavior (mechanical allodynia). Vector-mediated reduction in pain-related behavior was higher in magnitude and longer in duration after inoculation of the GAD-expressing vector than that achieved by the inoculation of the proenkephalin-expressing vector.


CONCLUSIONS
HSV-mediated gene transfer provides a novel method for treating chronic neuropathic pain related to lumbar root injury in rodents.
Lee
John Y K
JY
Penn Neurological Institute, PA Hospital, Philadelphia, PA, USA.
Fink
David J
DJ
Mata
Marina
M
D000818:Animals; D004745:Enkephalins / Q000235:genetics* / Q000494:pharmacology; D005528:Foot; D005727:Ganglia, Spinal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000494:pharmacology; D006941:Hyperesthesia / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008026:Ligation; D008161:Lumbosacral Region; D010146:Pain / Q000503:physiopathology*; D011498:Protein Precursors / Q000235:genetics* / Q000494:pharmacology; D011843:Radiculopathy / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000235:genetics; D013126:Spinal Nerve Roots
D004745:Enkephalins; D011498:Protein Precursors; C029992:proenkephalin; D005968:Glutamate Decarboxylase