The specific mechanism of migraine chronification remains unclear. We previously demonstrated that synaptic plasticity was associated with migraine chronification. EphB receptors and their ligands, ephrinBs, are considered to be key molecules regulating the synaptic plasticity of the central nervous system. However, whether they can promote the chronification of migraine by regulating synaptic plasticity is unknown. Therefore, we investigated the role of ephrinB/EphB signaling in chronic migraine (CM). Male Sprague-Dawley rats were used to construct a chronic migraine model by dural infusion of an inflammatory soup for 7 days. We used qPCR, western blot, and immunofluorescence to detect the mRNA and protein levels of EphB2 and ephrinB2. The paw withdrawal latency and paw withdrawal threshold were measured after lateral ventricle treatment with EphB1-Fc (an inhibitor of EphB receptor). Changes in synaptic plasticity were explored by examining synaptic-associated proteins by western blot, dendritic spines of neurons by Golgi-Cox staining, and synaptic ultrastructure by transmission electron microscopy. We found that the expression of EphB2 and ephrinB2 increased in CM. The administration of EphB1-Fc relieved hyperalgesia and changes in synaptic plasticity induced by CM. In addition, EphB1-Fc inhibited the upregulation of NR2B phosphorylation. These results indicate that ephrinB/EphB signaling may regulate synaptic plasticity in CM via NR2B phosphorylation, which suggests the novel idea that ephrinB/EphB signaling may be a target for the treatment of migraine chronification.

中文翻译：

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EphrinB / EphB信号通过NR2B磷酸化有助于慢性偏头痛的突触可塑性。

偏头痛同步化的具体机制仍不清楚。我们以前证明了，突触可塑性与偏头痛的时机性有关。EphB受体及其配体ephrinBs被认为是调节中枢神经系统突触可塑性的关键分子。但是，它们是否可以通过调节突触可塑性来促进偏头痛的发作。因此，我们调查了ephrinB / EphB信号传导在慢性偏头痛（CM）中的作用。通过硬脑膜注入炎性汤7天，使用雄性Sprague-Dawley大鼠构建慢性偏头痛模型。我们使用qPCR，蛋白质印迹和免疫荧光来检测EphB2和ephrinB2的mRNA和蛋白水平。在用EphB1-Fc（EphB受体抑制剂）进行侧脑室治疗后，测量足缩潜伏期和足缩阈值。通过Western印迹检查突触相关蛋白，通过Golgi-Cox染色检查神经元的树突棘以及通过透射电子显微镜检查突触超微结构，探索突触可塑性的变化。我们发现CM中EphB2和ephrinB2的表达增加。EphB1-Fc的使用可缓解痛觉过敏和CM诱导的突触可塑性变化。此外，EphB1-Fc抑制了NR2B磷酸化的上调。这些结果表明，ephrinB / EphB信号传导可能通过NR2B磷酸化调节CM中的突触可塑性，这表明ephrinB / EphB信号传导可能是治疗偏头痛时相的一个新思路。