Neurotrophic factors are highly potent macromolecules with protean effects. Although they are highly effective in vitro and in animal models in vivo, they have not been successfully applied to the treatment of human disease. Our laboratories have developed recombinant herpes simplex virus (HSV)-based vectors, that we have demonstrated may be used to deliver and express neurotrophic factor genes in dorsal root ganglion neurons to protect against the development of neuropathy in animal models, without causing systemic side effects. In a similar fashion, we have demonstrated that a vector expressing proenkephalin to mediate the release of opioid peptides from afferent nerve terminals in the spinal cord can be used to produce a localized antinociceptive effect in animal models of pain. Targeted gene delivery using HSV-based vectors offers a means to utilize short-lived peptides to produce specific effects in the nervous system.