Tumor necrosis factor-alpha contributes to below-level neuropathic pain after spinal cord injury.
OBJECTIVE
Our objective was to elucidate the mechanisms responsible for below-level pain after partial spinal cord injury (SCI).


METHODS
We used lateral hemisection to model central neuropathic pain and herpes simplex viral (HSV) vector-mediated transfer of the cleaved soluble receptor for tumor necrosis factor-alpha (TNF-alpha) to evaluate the role of TNF-alpha in the pathogenesis of below-level pain.


RESULTS
We found activation of microglia and increased expression of TNF-alpha below the level of the lesion in the lumbar spinal cord after T13 lateral hemisection that correlated with emergence of mechanical allodynia in the hind limbs of rats. Lumbar TNF-alpha had an apparent molecular weight of 27 kDa, consistent with the full-length transmembrane form of the protein (mTNF-alpha). Expression of the p55 TNF soluble receptor (sTNFRs) by HSV-mediated gene transfer resulted in reduced pain behavior and a decreased number of ED1-positive cells, as well as decreased phosphorylation of the p38 MAP kinase (p-p38) and diminished expression of mTNF-alpha in the dorsal horn.


CONCLUSIONS
These results suggest that expression of mTNF-alpha after injury is related to development of pain, and that reverse signaling through mTNF-alpha by sTNFR at that level reduces cellular markers of inflammatory response and pain-related behavior.
Peng
Xiang-min
XM
Department of Neurology, University of Michigan and VA Ann Arbor Healthcare System, 48109-0316, USA.
Zhou
Zhi-gang
ZG
Glorioso
Joseph C
JC
Fink
David J
DJ
Mata
Marina
M
D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D007150:Immunohistochemistry; D017628:Microglia; D010146:Pain / Q000209:etiology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics; D013119:Spinal Cord Injuries / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases