George A, Schmidt C, Weishaupt A, Toyka K V, Sommer C
Neurologische Universitätsklinik Würzburg, Germany.
Exp Neurol. 1999 Nov;160(1):124-32. doi: 10.1006/exnr.1999.7193.
Wallerian degeneration, induced after injury to a peripheral nerve, is associated with upregulation of proinflammatory cytokines, which are suggested to contribute to the development of lesion-induced neuropathic pain. In chronic constrictive injury (CCI), an animal model of injury-induced painful mononeuropathy, inhibition of synthesis, release, or function of the cytokine tumor necrosis factor-alpha (TNF) results in reduced pain-associated behavior. Here, changes of TNF content in rat sciatic nerves after CCI (days 0, 0.5, 1, 3, 7 and 14) were investigated by enzyme-linked-immunoassay. Low levels of TNF were already detectable in control nerves. Concentrations increased rapidly after CCI, with a maximum (2.7-fold) at 12 h, and remained elevated on a lower level until day 3. Baseline levels were reached again at day 14. These results indicate that TNF is produced at an early time point in the cascade of events resulting in Wallerian degeneration and hyperalgesia following peripheral nerve injury. Given that only prophylactic treatment with TNF inhibitors efficiently reduces hyperalgesia in CCI, TNF seems to contribute to the initiation of neuropathic pain in this model.
外周神经损伤后引发的沃勒变性与促炎细胞因子的上调有关，这些细胞因子被认为与损伤诱导的神经性疼痛的发展有关。在慢性压迫性损伤（CCI）这一损伤诱导的疼痛性单神经病变动物模型中，抑制细胞因子肿瘤坏死因子-α（TNF）的合成、释放或功能会导致疼痛相关行为减少。在此，通过酶联免疫吸附测定法研究了CCI后（第0、0.5、1、3、7和14天）大鼠坐骨神经中TNF含量的变化。在对照神经中已可检测到低水平的TNF。CCI后其浓度迅速升高，在12小时时达到最高值（2.7倍），并在较低水平维持升高直至第3天。在第14天再次达到基线水平。这些结果表明，在导致外周神经损伤后沃勒变性和痛觉过敏的一系列事件中，TNF在早期就会产生。鉴于只有用TNF抑制剂进行预防性治疗才能有效减轻CCI中的痛觉过敏，TNF似乎在该模型中促成了神经性疼痛的起始。
