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Abstract：
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.
摘要：
初步研究表明蝎子镇痛肽N58A对电压门控钠通道(VGSCs)具有显著作用,在神经病理性疼痛中发挥重要作用。目的探讨N58A对三叉神经痛(TN)的镇痛作用及其可能机制。结果表明，N58A能显著提高大鼠机械痛和热痛的阈值，抑制大鼠自发的不对称抓挠行为。免疫印迹结果显示,N58A能显著降低ERK1/2、P38、JNK、和ERK5/CREB通路以及Nav1.8和Nav1.9蛋白的表达呈剂量依赖性。用全细胞膜片钳技术检测TG神经元Nav1.8和Nav1.9通道的电流和动力学特征的变化。结果表明,N58A可显著降低模型大鼠Nav1.8和Nav1.9的电流密度,并将激活曲线移向超极化，将失活曲线移向去极化。总之,N58A对眶下慢性缩窄性损伤(IoN-CCI)模型大鼠的镇痛作用可能与MAPK通路和Nav1.8、Nav1.9钠通道的调节密切相关。
