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

白细胞介素-18（IL-18）是先天性和免疫应答的重要调节剂，并且已知其在各种类型的细胞中表达，并且在包括组织损伤和炎症的病理条件下上调，表明其具有促炎和代偿作用。在这里，我们表明，IL-18增加在三叉神经脊神经亚核尾侧（Vc）周围神经损伤后的小胶质细胞。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缩痛阈值显著降低，观察到IL-18在Obex区周围Vc的表达从神经损伤后3d开始显著增加，并持续到14 d。IL-18标记的细胞主要与Iba 1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的诱导表达与磷酸化p38 MAPK同时存在，提示p38可能参与了IL-1的调节。本研究首次报道三叉神经损伤诱导Vc区活化小胶质细胞IL-18的上调，提示IL-18可能在口面神经病理性疼痛中发挥作用。

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.