Efficiencies of Transgene Expression in Nociceptive Neurons Through Different Routes of Delivery of Adeno-Associated Viral Vectors

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Abstract
Transferring therapeutic genes into the nociceptive system, including dorsal root ganglia (DRGs) and the spinal cord, is potentially a powerful approach for the treatment of chronic pain in humans. Adeno-associated viral vectors (AAVs) are particularly useful in delivering foreign genes to targeted tissues because they seldom induce immune responses or produce cytotoxicity. To determine the efficiency of transgene expression and the best route(s) of delivery, a recombinant AAV type 2 vector containing the enhanced green fluorescent protein (EGFP) gene driven by the neuron-specific enolase (NSE) promoter (rAAV-EGFP) was constructed. We injected the vector into subcutaneous tissue, sciatic nerve, DRGs, and subarachnoid space, and examined EGFP expression in the DRG, spinal cord, and nerve fibers. Both sciatic nerve and DRG injection led to strong EGFP expression in a large number of DRG neurons. The expression persisted for more than 6-8 months. We then delivered the μ-opioid receptor (μOR) gene into DRGs through direct DRG or sciatic nerve injection of rAAV-μOR and found a significant increase in morphine efficacy. These results suggest that delivering therapeutic genes to DRGs by the rAAV-NSE vector is a valid strategy for treatment of chronic pain.