METHODS: Here, we used intraperitoneal injection of glyceryl trinitrate (GTN, 10 mg/kg) as a migraine mouse model, which was verified by light-aversive test, von Frey test, and elevated plus maze test. We then performed whole-brain imaging with NPY-GFP mice to explore the critical regions where NPY was changed by GTN treatment. Next, we microinjected NPY into the medial habenula (MHb), and further infused Y1 or Y2 receptor agonists into the MHb, respectively, to detect the effects of NPY in GTN-induced migraine-like behaviors.
RESULTS: GTN effectively triggered allodynia, photophobia, and anxiety-like behaviors in mice. After that, we found a decreased level of GFP+ cells in the MHb of GTN-treated mice. Microinjection of NPY attenuated GTN-induced allodynia and anxiety without affecting photophobia. Furthermore, we found that activation of Y1-but not Y2-receptors attenuated GTN-induced allodynia and anxiety.
CONCLUSIONS: Taken together, our data support that the NPY signaling in the MHb produces analgesic and anxiolytic effects through the Y1 receptor. These findings may provide new insights into novel therapeutic targets for the treatment of migraine.
方法:这里,我们使用腹腔注射硝酸甘油酯(GTN,10mg/kg)作为偏头痛小鼠模型,通过光线厌恶测试验证了这一点,冯·弗雷测试,和高架加迷宫测试。然后,我们用NPY-GFP小鼠进行全脑成像,以探索通过GTN治疗改变NPY的关键区域。接下来,我们将NPY显微注射到内囊(MHb)中,并进一步将Y1或Y2受体激动剂注入MHb,分别,检测NPY在GTN诱导的偏头痛样行为中的作用。
结果:GTN有效触发异常性疼痛,畏光,和老鼠的焦虑样行为。之后,我们发现GTN处理小鼠的MHb中GFP+细胞水平降低。NPY的显微注射减轻了GTN诱导的异常性疼痛和焦虑,而不影响畏光。此外,我们发现激活Y1-而非Y2-受体可减弱GTN诱导的异常性疼痛和焦虑。
结论:综合来看,我们的数据支持MHb中的NPY信号通过Y1受体产生镇痛和抗焦虑作用.这些发现可能为偏头痛的治疗提供新的治疗靶点。