title: Experimental autoimmune encephalomyelitis-induced upregulation of tumor necrosis factor-alpha in the dorsal root ganglia.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a chronic, neurological disease characterized by targeted destruction of 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 (TNFalpha) 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 TNFalpha expression in the DRG and of EAE animals at peak disease stage, as assessed by clinical symptoms.
  
  
  CONCLUSIONS
  Antigen-induced production of inflammatory cytokines such as TNFalpha within the DRG identifies a potential novel mechanism for MS-induced NPP.
authors: Faculty of Pharmacy, Apotex Centre, University of Manitoba, Winnipeg, MB, Canada.
authors: M
authors: M
authors: Melanson
authors: P
authors: P
authors: Miao
authors: D
authors: D
authors: Eisenstat
authors: Y
authors: Y
authors: Gong
authors: X
authors: X
authors: Gu
authors: K
authors: K
authors: Au
authors: W
authors: W
authors: Zhu
authors: F
authors: F
authors: Begum
authors: E E
authors: EE
authors: Frost
authors: M
authors: M
authors: Namaka
mesh_terms: D000818:Animals; D004185:Disability Evaluation; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D015870:Gene Expression; D007150:Immunohistochemistry; D009103:Multiple Sclerosis / Q000150:complications / Q000378:metabolism; D010146:Pain / Q000209:etiology; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014584:User-Computer Interface
chemical_list: D014409:Tumor Necrosis Factor-alpha