Analysis of the communication-of-information system through glial cell in trigeminal ganglion

白介素18(IL-18)是天然免疫反应的重要调节因子，在多种细胞中均有表达，在组织损伤和炎症等病理条件下表达上调，具有促炎和代偿作用。本研究显示，周围神经损伤后，三叉神经脊束核尾侧亚核(Vc)的小胶质细胞中IL-18的表达增加。我们采用三叉神经病理性疼痛模型，切断下牙槽神经后，上颌须垫皮肤的抽离阈值显著降低，IL-18在OBEX区周围的VC中的表达从3d开始显著增加，并持续到神经损伤后14d。IL-18标记细胞主要与Iba1共定位，提示这种上调发生在过度活跃的小胶质细胞中。我们还发现IL-18的诱导与磷酸化的p38MAPK并存，提示p38可能在IL-1的调节中起作用。我们的发现是三叉神经损伤诱导Vc内激活的小胶质细胞IL-18上调的首次报道，提示IL-18可能在口面神经病理性疼痛中起作用。

Interleukin -18 (IL-18) is an important regulator of innate and immune responses, and is known to be expressed in various types of cells and upregulated in pathological conditions including tissue injury and inflammation, suggesting it has both proinflammatory and compensatory roles. Here we show that IL-18 was increased in microglia in the trigeminal spinal subnucleus caudalis (Vc) after peripheral nerve injury. We used a trigeminal neuropathic pain model in which the withdrawal threshold of maxillary whisker pad skin was significantly decreased after inferior alveolar nerve transection, and observed a striking increase in IL-18 expression in the Vc around the obex area from3d and continued until 14d after nerve injury. The IL-18 labeled cells were largely colocalized with Iba1, suggesting this upregulation occurred in hyperactive microglia. We also found that the IL-18 induction coexisted with phosphorylated p38 MAPK, indicating a possible role of p38 in the regulation of IL-1.Our findings are the first report that injury of trigeminal nerve induced IL-18 upregulation in activated microglia in theVc, suggesting a possible role of IL-18 in orofacial neuropathic pain.