Hippocampal AMPARs involve the central sensitization of rats with irritable bowel syndrome.

Aiqin Chen,Chun Lin,Zizhi Cui,Chengjia Bao,Yu Chen,Meng Xiao,Ying Tang

doi:10.1002/brb3.650

Abstract

ObjectiveThe roles of hippocampal AMPARs were investigated in irritable bowel syndrome (IBS)‐like rats to clarify the central sensitization mechanisms.Methods IBS model was induced by neonatal maternal separation. The effects of AMPARs on visceral hypersensitivity were examined by the responses of abdominal muscle to colorectal distension after the bilateral intrahippocampal injections of CNQX (an AMPAR inhibitor). The expressions of hippocampal AMPARs (GluR1 and GluR2) were determined by Western blot.ResultsThe IBS‐like rats showed visceral hypersensitivity when compared with controls. Bilateral intrahippocampal injections of CNQX alleviated the visceral pain in IBS‐like rats. The maximal effect appeared at the time point of 30 min, and the duration lasted for 90 min after CNQX application, under 40 and 60 mmHg CRD. The expressions of hippocampal GluR2 significantly increased in IBS‐like rats when compared with controls (p < .05). However, the levels of hippocampal GluR1 had no significant differences in rats. Hippocampal LTP induced by HFS was significantly enhanced when compared with controls (p < .05). The expressions of GluR2 significantly increased in the control and IBS‐like rats after 60 min LTP of recordings (p < .05), but not GluR1.ConclusionNeonatal maternal separation enhances the expression of GluR2 and facilitates the LTP in the hippocampus, which could lead to the formation of visceral hypersensitivity when grown up.

Highlights

Irritable bowel syndrome (IBS) influences around 11% of the population globally (Canavan, West, & Card, 2014)
We found that hippocampal GluR2 may contribute to the enhanced LTP and induce visceral hypersensitivity in irritable bowel syndrome (IBS)-like rats
Our results are in accordance with those of Lin (Lin & Al-Chaer, 2005): low, medial, and high doses of CNQX all significantly decreased the neuronal responses to colorectal distension (CRD) in IBS-like rats

Summary

| INTRODUCTION

Irritable bowel syndrome (IBS) influences around 11% of the population globally (Canavan, West, & Card, 2014) It manifests as abdominal hypersensitivity and abnormal gastrointestinal function. Most researches about the mechanism of visceral hypersensitivity focused on peripheral sensitization and the synaptic plasticity change in cornu dorsal medullae spinalis. Chronic pain lasts after the damage has cured It is because of the functional or structural changes in the brain like memory processes. A greater number of researchers believe that chronic pain shares a similar mechanism with memory, i.e., long-term potentiation. Our previous results suggest that spinal AMPARs may participate in the process of central hypersensitivity (Lin & Al-Chaer, 2005), but the roles of hippocampal AMPARs in chronic visceral pain remain unclear. A plausible mechanism of central hypersensitivity of chronic visceral pain in IBS was raised

| MATERIAL AND METHODS

Findings

| DISCUSSION