Zhai QingLing, Wang KaiXin, Zhang Defu, Chen Jinbo, Dong XiaoMeng, Pan Yonghui
Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Neurology, The Third Hospital of Jinan Shandong, Jinan, China.
Korean J Pain. 2023 Jul 1;36(3):335-346. doi: 10.3344/kjp.23039.
Perampanel, 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 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.
Perampanel treatment notably increased the mechanical withdrawal threshold and decreased head grooming and light-aversive behaviors in NTG-treated rats. It also decreased PACAP expression and affected cAMP/PKA/CREB signaling pathway. However, PLC/PKC signaling pathway may not be involved in this treatment. In studies, perampanel notably decreased PACAP expression by inhibiting cAMP/PKA/CREB signaling pathway.
This study shows that perampanel inhibits the migraine-like pain response and that this beneficial effect might be attributable to regulation of the cAMP/PKA/CREB signaling pathway.
吡仑帕奈是一种高选择性的谷氨酸AMPA受体拮抗剂，广泛用于治疗癫痫。鉴于癫痫和偏头痛之间存在共同的病理生理特征，本研究旨在探讨吡仑帕奈是否能发挥抗偏头痛作用。
使用硝酸甘油（NTG）诱导大鼠偏头痛模型，模型动物分别用50μg/kg和100μg/kg的吡仑帕奈进行预处理。通过蛋白质印迹法和定量实时PCR对三叉神经节中垂体腺苷酸环化酶激活多肽（PACAP）的表达进行定量，并采用大鼠特异性酶联免疫吸附测定法检测血清中的表达。还进行了蛋白质印迹法，以探讨吡仑帕奈治疗对磷脂酶C（PLC）/蛋白激酶C（PKC）和蛋白激酶A（PKA）/cAMP反应元件结合蛋白（CREB）信号通路的影响。此外，通过刺激海马神经元评估cAMP/PKA/CREB依赖性机制。将细胞用吡仑帕奈、拮抗剂和激动剂处理24小时，制备细胞裂解物用于蛋白质印迹分析。
吡仑帕奈治疗显著提高了NTG处理大鼠的机械撤足阈值，并减少了头部梳理和避光行为。它还降低了PACAP的表达并影响了cAMP/PKA/CREB信号通路。然而，PLC/PKC信号通路可能不参与此治疗。在研究中，吡仑帕奈通过抑制cAMP/PKA/CREB信号通路显著降低了PACAP的表达。
本研究表明，吡仑帕奈可抑制偏头痛样疼痛反应，这种有益作用可能归因于对cAMP/PKA/CREB信号通路调节。
