Vector-Mediated Gene Transfer to Express Inhibitory Neurotransmitters in Dorsal Root Ganglion Reduces Pain in a Rodent Model of Lumbar Radiculopathy

In Brief Study Design. A prospective in vivo animal study. Objectives. 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. 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. Transfer of the genes coding for proenkephalin or glutamic acid decarboxylase to dorsal root ganglion in vivo, achieved by subcutaneous inoculation of nonreplicating herpes simplex virus-based vector, reduced pain-related behavior in the L5 dorsal root ligation model of lumbar radiculopathy in the rat.