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

Abstract

A prospective in vivo animal study. 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. 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. 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.