Upregulation of Spinal ASIC1 and NKCC1 Expression Contributes to Chronic Visceral Pain in Rats.

Yong-Chang Li,Ping-An Zhang,Yuan-Qing Tian,Jie Sha,Yan-Yan Wu,Guang-Yin Xu,Yu-Cheng Xu

doi:10.3389/fnmol.2020.611179

Abstract

Aims: To determine whether acid-sensing ion channel 1 (ASIC1)–sodium-potassium-chloride cotransporter 1 (NKCC1) signaling pathway participates in chronic visceral pain of adult rats with neonatal maternal deprivation (NMD).Methods: Chronic visceral pain was detected by colorectal distension (CRD). Western blotting and Immunofluorescence were performed to detect the expression and location of ASIC1 and NKCC1. Whole-cell patch-clamp recordings were performed to record spinal synaptic transmission.Results: The excitatory synaptic transmission was enhanced and the inhibitory synaptic transmission was weakened in the spinal dorsal horn of NMD rats. ASIC1 and NKCC1 protein expression in the spinal dorsal horn was significantly up-regulated in NMD rats. Incubation of Amiloride reduced the amplitude of mEPSCs. Incubation of Bumetanide (BMT) increased the amplitude of mIPSCs. Intrathecal injection of ASIC1 or NKCC1 inhibitors reversed the threshold of CRD in NMD rats. Also, Amiloride treatment significantly reversed the expression of NKCC1 in the spinal dorsal horn of NMD rats.Conclusion: Our data suggest that the ASIC1-NKCC1 signaling pathway is involved in chronic visceral pain in NMD rats.

Highlights

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence
We demonstrated that the simulation of the neonatal maternal deprivation (NMD) induced chronic visceral pain in adult rats, which is consistent with the published articles from our lab and others (Chen et al, 2017; Du et al, 2019; Li et al, 2020)
We showed that both acid-sensing ion channel 1 (ASIC1) and NKCC1 in the spinal dorsal horn were involved in chronic visceral pain via increased excitatory synaptic transmission in the NMD rats

Summary

Introduction

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. It is characterized by chronic abdominal pain and altered bowel movements (Enck et al, 2016; Raskov et al, 2016). There is a lack of effective treatment for the chronic visceral pain hypersensitivity associated with IBS due to the unclear underlying pathogenesis. It is urgent to explore the detailed mechanisms leading to develop effective targets for the treatment of visceral pain. The regulation of visceral pain sensitivity at the spinal cord level is rarely reported, so the mechanism remains largely unclear

Methods

Results

Conclusion