Peng Xiang-min, Zhou Zhi-gang, Glorioso Joseph C, Fink David J, Mata Marina
Department of Neurology, University of Michigan and VA Ann Arbor Healthcare System, 48109-0316, USA.
Ann Neurol. 2006 May;59(5):843-51. doi: 10.1002/ana.20855.
Our objective was to elucidate the mechanisms responsible for below-level pain after partial spinal cord injury (SCI).
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.
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.
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.
我们的目的是阐明脊髓部分损伤（SCI）后损伤平面以下疼痛的发病机制。
我们采用侧方半横切来模拟中枢神经性疼痛，并通过单纯疱疹病毒（HSV）载体介导的肿瘤坏死因子-α（TNF-α）裂解可溶性受体的转移，来评估TNF-α在损伤平面以下疼痛发病机制中的作用。
我们发现，在T13侧方半横切后，腰段脊髓损伤平面以下的小胶质细胞被激活，TNF-α表达增加，这与大鼠后肢出现机械性异常疼痛相关。腰段TNF-α的表观分子量为27 kDa，与该蛋白的全长跨膜形式（mTNF-α）一致。HSV介导的基因转移导致p55 TNF可溶性受体（sTNFRs）表达，从而使疼痛行为减轻，ED1阳性细胞数量减少，同时背角中p38丝裂原活化蛋白激酶（p-p38）的磷酸化减少，mTNF-α的表达降低。
这些结果表明，损伤后mTNF-α的表达与疼痛的发生发展有关，并且该水平的sTNFR通过mTNF-α的反向信号传导可减少炎症反应的细胞标志物和疼痛相关行为。
