Tumor necrosis factor–α contributes to below‐level neuropathic pain after spinal cord injury

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Abstract
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–α (TNF-α) to evaluate the role of TNF-α in the pathogenesis of below-level pain. Results We found activation of microglia and increased expression of TNF-α 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-α had an apparent molecular weight of 27kDa, consistent with the full-length transmembrane form of the protein (mTNF-α). 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-α in the dorsal horn. Interpretation These results suggest that expression of mTNF-α after injury is related to development of pain, and that reverse signaling through mTNF-α by sTNFR at that level reduces cellular markers of inflammatory response and pain-related behavior. Ann Neurol 2006;59:843–851

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