(93n) Microparticle Mediated Delivery of Protein for Treatment of Chronic Pain

Neural cells have been thought to be the main cause of allodynia, or neuropathic pain. While neural cells are critical, glial cells also seem to play an important role. Targeting glial cells with therapeutic genes and proteins partially reverses allodynia in animal models. Interleukin-10 (IL-10) and Brain-Derived Neurotrophic Factor (BDNF) have been shown to transiently reverse allodynia in animal models. Previous limitations with protein delivery include a short protein half life, which limits reversal to 24 hours. Injections of plasmid DNA are more effective in the long term; however they currently require dosages of DNA outside of the practical administration range. Administering DNA through a viral vector is only effective for a one week period, after which point the immune system detects and destroys the infected cells. Protein PEGylaltion and microparticle encapsulation of DNA are promising methods for reducing the necessary amount of plasmid DNA and increasing a protein's half-life. Intrathecal injection of microparticle encapsulated pDNA for IL-10 causes a long-term reversal, while the direct administration of BDNF protein causes a transient reversal. These studies show that administration of protein leads to therapeutic effect, and that long term release of protein either through injection or gene therapy is best.