A prospective in vivo
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
Summary of Background Data.
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 γ-aminobutyric acid. HSV-mediated gene transfer of proenkephalin or GAD to DRG reduces pain
-related behavior in rodent models of peripheral neuropathic pain
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.
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.
HSV-mediated gene transfer provides a novel method for treating chronic neuropathic pain
related to lumbar root injury in rodents.