10.7910/DVN/Y7VYUQQingLing ZhaiDepartment of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKaiXin WangDepartment of Neurology, The Third Hospital of Jinan Shandong, ChinaDefu ZhangDepartment of Neurology, Shengli Oilfield Central Hospital, Shandong, ChinaJinbo ChenDepartment of Neurology, Binzhou Medical University Hospital, Shandong, ChinaXiaoMeng DongDepartment of Neurology, Binzhou Medical University Hospital, Shandong, ChinaYonghui PanDepartment of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, ChinaHarvard Dataverse2023Medicine, Health and Life SciencesChronic PainCyclic AMP-Dependent Protein KinasesGlutamateHippocampusHyperalgesiaMigraine DisordersNitroglycerinPerampanelPituitary Adenylate Cyclase-Activating PolypeptideRatsReceptors, AMPAYonghui PanDepartment of Neurology, First Affiliated Hospital of Harbin Medical University2023-06-272023-06-2710.3344/kjp.2303939241application/vnd.openxmlformats-officedocument.spreadsheetml.sheet1.0CC0 1.0Perampanel, a highly selective glutamate AMPA receptor antagonist, is widely used to treat epilepsy. Since the existence of common pathophysiological features between epilepsy and migraine, the aim of this study was to investigate whether perampanel could exert an antimigraine effect. Nitroglycerin (NTG) was used to induce a migraine model in rats, and the model animals were pretreatment with 50 μg/kg and 100 μg/kg perampanel. The expression of pituitary adenylate-cyclase-activating polypeptide (PACAP) was quantified by western blot and quantitative real-time PCR in the trigeminal ganglion, and rat-specific enzyme-linked immunosorbent assay in serum. Western blot was also conducted to explore the effects of perampanel treatment on the phospholipase C (PLC)/protein kinase C (PKC) and protein kinase A (PKA)/ cAMP-responsive-element-binding protein (CREB) signaling pathways. Moreover, the cAMP/PKA/CREB-dependent mechanism was evaluated via in vitro stimulation of hippocampal neurons. The cells were treated with perampanel, antagonists and agonists for 24 hours and cell lysates were prepared for western blot analysis.