Experimental autoimmune encephalomyelitis-induced upregulation of tumor necrosis factor-alpha in the dorsal root ganglia.
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.
Melanson
M
M
Faculty of Pharmacy, Apotex Centre, University of Manitoba, Winnipeg, MB, Canada.
Miao
P
P
Eisenstat
D
D
Gong
Y
Y
Gu
X
X
Au
K
K
Zhu
W
W
Begum
F
F
Frost
E E
EE
Namaka
M
M
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
D014409:Tumor Necrosis Factor-alpha