NeuroBiotechnology: A new tool in peripheral nervous system and painful neuropathy

Neoplastic lesions, infections or injury in the face may result in the loss of structure and function of maxillofacial tissues. The mission of the UCLA Weintraub Center is to improve the quality of life of these patients through novel therapeutic modalities. After removal of teeth or jaw tissues, patients may experience neuropathic chronic pain, which can significantly degrade the quality of life. Descriptive studies on humans and animal models have indicated that the upregulation of NaV1.8 tetrodotoxin-resistant sodium channel functional expression seems to associate with the pathogenesis of neuropathy. We have further demonstrated an increase of NaV1.8 mRNA in the nerve, not in the dorsal root ganglia (DRG), in rats exhibiting painful neuropathy due to sciatic nerve entrapment (SNE). However, the lack of adequate tools to manipulate the expression of specific gene product in the peripheral nervous system has presented a challenge for mechanistic investigation of painful neuropathy. To overcome this problem, we have devised cationized gelatin-plasmid DNA (CG/DNA) polyplex nanoparticles as a gene transfer platform to peripheral sensory neurons. After subcutaneous injection to rat hind paw, CG/DNA generated an unexpectedly robust reporter gene expression in L4/L5 DRG through sciatic nerve retrograde transfer. With this new tool, we are currently investigating the pathological mechanism and the role of NaV1.8 in the rat SNE painful neuropathy model. The outcome of these studies has already indicated several therapeutic targets.