Abstract：
Trigeminal neuralgia (TN) is a common type of peripheral neuralgia in clinical practice, which is usually difficult to cure. Common analgesic drugs are difficult for achieving the desired analgesic effect. Syb-prII-1 is a β-type scorpion neurotoxin isolated from the scorpion venom of Buthus martensi Karsch (BmK). It has an important influence on the voltage-gated sodium channel (VGSCs), especially closely related to Nav1.8 and Nav1.9. To explore whether Syb-prII-1 has a good analgesic effect on TN, we established the Sprague Dawley (SD) rats\' chronic constriction injury of the infraorbital nerve (IoN-CCI) model. Behavioral, electrophysiological, Western blot, and other methods were used to verify the model. It was found that Syb-prII-1 could significantly relieve the pain behavior of IoN-CCI rats. After Syb-prII-1 was given, the phosphorylation level of the mitogen-activated protein kinases (MAPKs) pathway showed a dose-dependent decrease after IoN-CCI injury. Moreover, Syb-prII-1(4.0 mg/kg) could significantly change the steady-state activation and inactivation curves of Nav1.8. The steady-state activation and inactivation curves of Nav1.9 were similar to those of Nav1.8, but there was no significant difference. It was speculated that it might play an auxiliary role. The binding mode, critical residues, and specific interaction type of Syb-prII-1 and VSD2rNav1.8 were clarified with computational simulation methods. Our results indicated that Syb-prII-1 could provide a potential treatment for TN by acting on the Nav1.8 target.
摘要：
三叉神经痛(TN)是临床上常见的一种外周神经痛,通常很难治愈。常见的镇痛药物很难达到理想的镇痛效果。Syb-prII-1是从ButhusmartensiKarsch（BmK）的蝎毒中分离出的β型蝎子神经毒素。它对电压门控钠通道（VGSCs）有重要影响，特别是与Nav1.8和Nav1.9密切相关。探讨Syb-prII-1对TN是否有良好的镇痛作用,我们建立了SpragueDawley（SD）大鼠眶下神经慢性压迫性损伤（IoN-CCI）模型。行为,电生理学,蛋白质印迹,等方法对模型进行了验证。发现Syb-prII-1可以显着缓解IoN-CCI大鼠的疼痛行为。给予Syb-prII-1后，在IoN-CCI损伤后,丝裂原活化蛋白激酶(MAPKs)途径的磷酸化水平呈剂量依赖性下降.此外，Syb-prII-1(4.0mg/kg)可以显著改变Nav1.8的稳态激活和失活曲线。Nav1.9的稳态激活和失活曲线与Nav1.8相似，但无显著差异。据推测，它可能起到辅助作用。绑定模式，临界残基,用计算模拟方法阐明了Syb-prII-1和VSD2rNav1.8的特定相互作用类型。我们的结果表明，Syb-prII-1可以通过作用于Nav1.8靶标为TN提供潜在的治疗。
