NeuroImmune modulation of multiple sclerosis via the dorsal root ganglia

Abstract

Background: Multiple sclerosis (MS) is a chronic, neurological disease characterized by targeted destruction on central nervous system (CNS) myelin. The autoimmune theory is the most widely accepted explanation of disease pathology. Circulating Th-1 cells become activated by exposure to CNS-specific antigens such as myelin basic protein. The activated Th-1 cells secrete inflammatory cytokines, which are pivotal for inflammatory responses. We hypothesize that enhanced production of inflammatory cytokines triggers cellular events within the dorsal root ganglia (DRG) and/or spinal cord, facilitating the development of neuropathic pain (NPP) in MS. NPP, the second worst disease-induced symptom suffered by patients with MS, is normally regulated by DRG and/or spinal cord. Objective: To determine gene and protein expression levels of tumor necrosis factor-alpha (TNF ) within DRG and/or spinal cord in an animal model of MS. Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in adolescent female Lewis rats. Animals were sacrificed every 3 days post-disease induction. DRG and spinal cords were harvested for protein and gene expression analysis. Results: We show significant increases in TNF expression in the DRG and of EAE animals at peak disease stage, as assessed by clinical symptoms. Conclusion: Antigen-induced production of inflammatory cytokines such as TNF within the DRG identifies a potential noel mechanism for MS-induced NPP.