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

白细胞介素-18 （IL-18）是先天和免疫反应的重要调节因子，已知在各种类型的细胞中表达，并在组织损伤和炎症等病理条件下上调，表明它具有促炎和代偿作用。我们发现，周围神经损伤后，三叉神经脊髓尾侧亚核（Vc）的小胶质细胞中IL-18水平升高。我们采用三叉神经性疼痛模型，下肺泡神经横断后上颌须垫皮肤的戒断阈值明显降低，并观察到神经损伤后第3天至第14天，上颌须垫周围Vc中IL-18表达显著升高。IL-18标记的细胞大部分与Iba1共定位，表明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诱导与磷酸化的p38 MAPK共存，这表明p38可能在调节IL-1中发挥作用。我们的研究结果是首次报道三叉神经损伤诱导vc中活化小胶质细胞IL-18上调，提示IL-18可能在口面神经性疼痛中起作用。

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.