Abstract: This invention relates to methods and compositions for overcoming the dose-dependent down regulation of interleukin 10 (IL-10) by expressing, in addition to an interleukin 10 (IL-10) peptide, an IL-10 receptor type 1 (IL-10R1) peptide. The methods have use in treating a variety of diseases and symptoms, including but not limited to neuropathic or chronic pain; symptoms and physiological damage associated with multiple sclerosis, spinal cord injury, ALS, neuroinflammation, arthritis and other diseases of the joint; and autoimmune diseases.

Abstract: Methods of delivering transgenes to target cells using plasmids comprising viral inverted terminal repeat (ITR) sequences are described. Such plasmids are capable of directing sustained transgene expression in target cells in rats provided that at least one adeno-associated virus (AAV) ITR sequence is present in the plasmid, regardless of whether that ITR is located upstream or downstream of the transgene. In a particular embodiment, plasmids comprising one or more AAV ITR sequence and an IL-10 transgene are shown to be effective in sustained reversal of pain in an animal model of neuropathic pain.

Abstract: Compositions and methods for the treatment of neuropathic pain are provided. Compositions of the invention may comprise proteins with a zinc-finger domain fused to a regulatory domain that is capable of either activating or repressing the expression of a target gene involved in neuropathic pain. Alternatively, compositions of the invention may comprise a nucleic acid sequence encoding a protein of the invention, which nucleic acid sequence may optionally be provided as a plasmid or within a virus or other vector for delivery to a target cell or tissue. Methods of treating neuropathic pain involving treatment of subject with the compositions of the invention are also provided. Exemplary target genes for the treatment of neuropathic pain include VR1, NaV1.8, and TrkA.