Vasudeva Kiran, Vodovotz Yoram, Azhar Nabil, Barclay Derek, Janjic Jelena M, Pollock John A
Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282, USA; Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA 15282, USA.
Department of Surgery and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
J Neuroimmunol. 2015 Jun 15;283:43-9. doi: 10.1016/j.jneuroim.2015.04.012. Epub 2015 Apr 28.
Inflammation is associated with peripheral neuropathy, however the interplay among cytokines, chemokines, and neurons is still unclear. We hypothesized that this neuroinflammatory interaction can be defined by computational modeling based on the dynamics of protein expression in the sciatic nerve of rats subjected to chronic constriction injury. Using Dynamic Bayesian Network inference, we identified interleukin (IL)-18 as a central node associated with neuropathic pain in this animal model. Immunofluorescence supported a role for inflammasome activation and induction of IL-18 at the site of injury. Combined in vivo and in silico approaches may thus highlight novel targets in peripheral neuropathy.
炎症与周围神经病变相关,然而细胞因子、趋化因子和神经元之间的相互作用仍不清楚。我们推测,这种神经炎症相互作用可以通过基于慢性压迫性损伤大鼠坐骨神经中蛋白质表达动态的计算模型来定义。使用动态贝叶斯网络推理,我们确定白细胞介素(IL)-18是该动物模型中与神经性疼痛相关的中心节点。免疫荧光证实了炎性小体激活和损伤部位IL-18诱导的作用。因此,体内和计算机模拟相结合的方法可能会揭示周围神经病变中的新靶点。