Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang 110016, China.
Toxins (Basel). 2021 May 17;13(5):357. doi: 10.3390/toxins13050357.
The primary studies have shown that scorpion analgesic peptide N58A has a significant effect on voltage-gated sodium channels (VGSCs) and plays an important role in neuropathic pain. The purpose of this study was to investigate the analgesic effect of N58A on trigeminal neuralgia (TN) and its possible mechanism. The results showed that N58A could significantly increase the threshold of mechanical pain and thermal pain and inhibit the spontaneous asymmetric scratching behavior of rats. Western blotting results showed that N58A could significantly reduce the protein phosphorylation level of ERK1/2, P38, JNK, and ERK5/CREB pathways and the expression of Nav1.8 and Nav1.9 proteins in a dose-dependent manner. The changes in current and kinetic characteristics of Nav1.8 and Nav1.9 channels in TG neurons were detected by the whole-cell patch clamp technique. The results showed that N58A significantly decreased the current density of Nav1.8 and Nav1.9 in model rats, and shifted the activation curve to hyperpolarization and the inactivation curve to depolarization. In conclusion, the analgesic effect of N58A on the chronic constriction injury of the infraorbital (IoN-CCI) model rats may be closely related to the regulation of the MAPK pathway and Nav1.8 and Nav1.9 sodium channels.
初步研究表明，蝎镇痛肽 N58A 对电压门控钠离子通道（VGSCs）有显著影响，并在神经性疼痛中发挥重要作用。本研究旨在探讨 N58A 对三叉神经痛（TN）的镇痛作用及其可能的机制。结果表明，N58A 可显著提高机械痛和热痛的阈值，并抑制大鼠自发性不对称搔抓行为。Western blot 结果显示，N58A 可显著降低 ERK1/2、P38、JNK 和 ERK5/CREB 通路的蛋白磷酸化水平以及 Nav1.8 和 Nav1.9 蛋白的表达，且呈剂量依赖性。通过全细胞膜片钳技术检测 TG 神经元中 Nav1.8 和 Nav1.9 通道的电流和动力学特性变化。结果表明，N58A 可显著降低模型大鼠 Nav1.8 和 Nav1.9 的电流密度，并使激活曲线向超极化方向偏移，失活曲线向去极化方向偏移。综上所述，N58A 对眶下神经慢性缩窄损伤（IoN-CCI）模型大鼠的镇痛作用可能与 MAPK 通路和 Nav1.8、Nav1.9 钠离子通道的调节密切相关。
