N58A Exerts Analgesic Effect on Trigeminal Neuralgia by Regulating the MAPK Pathway and Tetrodotoxin-Resistant Sodium Channel.

Chun-Li Li,Ran Yang,Yang Sun,Yuan Feng,Yong-Bo Song

doi:10.3390/toxins13050357

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.

Highlights

Trigeminal neuralgia (TN) is a clinically typical chronic neurological disease
All human voltage-gated sodium channels (VGSCs) subtypes have more than 75% amino acid sequence identity, and each VGSC subtype is distributed in cells and tissues, indicating that it can be studied by anesthesia or selecting a specific region of VGSC
CREB-dependent gene expression is believed to be related to central sensitization associated with persistent pain states [5]. These findings indicate that the ERK5/CREB pathway plays a vital role in both inflammatory pain and neuropathic pain

Summary

Introduction

The International Association for the Study of Pain (IASP) defines it as sudden, severe, transient, severe, often unilateral, acupuncture-like, recurrent neuropathic pain in one or more branches of the trigeminal nerve. It can be caused by a light touch on the face, such as touching, eating, talking, washing the face, or slight irritation such as natural wind [1]. VGSC is closely related to neuropathic pain and inflammatory pain. The subtypes of VGSC can be divided into two types according to their sensitivity to tetrodotoxin (TTX). Sodium channels are closely related to neuropathic pain and inflammatory pain. VGSC is involved in the transmission of pain stimuli in the sensory nerves, suggesting its great potential in the development of new analgesics

Objectives

Methods

Results

Conclusion