Related Experiment Video
Updated: Jul 16, 2025
Investigating Intestinal Barrier Breakdown in Living Organoids
Published on: March 26, 2020
Lidocaine ameliorates intestinal barrier dysfunction in irritable bowel syndrome by modulating
Yanrong Wang1, Mingbiao Qiao2, Xue Yao3
1Department of Laboratory Medicine, Sichuan Tianfu New Area People's Hospital, Chengdu, China.
Background:
Intestinal barrier dysfunction is a prevalent pathogenic factor underlying various disorders. Currently there is no effective resolution. Previous studies have reported the potential anti-inflammatory properties of lidocaine and its ability to alleviate visceral hypersensitivity in individuals with irritable bowel syndrome (IBS). Therefore, our study will further verify the effect of lidocaine on intestinal barrier dysfunction in IBS and investigate the underlying mechanisms.
Methods:
In this study, we investigated the role of lidocaine by assessing visceral hypersensitivity, body weight, inflammatory factors, fluorescein isothiocyanate-dextran 4000 (FD4) flux, tight junctions (TJs) and spleen and thymus index in rats subjected to water avoidance stress (WAS) to mimic intestinal barrier dysfunction in IBS with and without lidocaine. In vitro, we investigated the role of corticotropin-releasing hormone receptor 2 (CRHR2) in lidocaine-treated Caco2 cells using small interfering RNA (siRNA) targeting CRHR2.
Key Results:
In WAS rats, lidocaine significantly restored weight loss, damaged TJs, spleen index and thymus index and inhibited abdominal hypersensitivity as well as blood levels of markers indicating intestinal permeability, such as diamine oxidase (DAO), D-lactic acid (D-Lac) and lipopolysaccharide (LPS). Consequently, the leakage of FD4 flux from intestine was significantly attenuated in lidocaine group, and levels of intestinal inflammatory factors (IL-1β, IFN-γ, TNF-α) were reduced. Interestingly, lidocaine significantly suppressed corticotropin-releasing hormone (CRH) levels in lamina propria cells, while the CRH receptor CRHR2 was upregulated in intestinal epithelial cells. In vitro, lidocaine enhanced the expression of CRHR2 on Caco-2 intestinal epithelial cells and restored disrupted TJs and the epithelial barrier caused by LPS. Conversely, these effects were diminished by a CRHR2 antagonist and siRNA-CRHR2, suggesting that the protective effect of lidocaine depends on CRHR2.
Conclusions And Inferences:
Lidocaine ameliorates intestinal barrier dysfunction in IBS by potentially modulating the expression of CRHR2 on intestinal epithelial cells.
Related Concept Videos
01:17Drugs for Treatment of Diarrhea-Predominant IBS
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
01:21Drugs for Treatment of Constipation-Predominant IBS
01:17Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents
Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down...
01:17Irritable Bowel Syndrome I: Introduction
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
01:30Irritable Bowel Syndrome II: Clinical Features and Diagnostic Evaluation
Irritable Bowel Syndrome (IBS) is classified into subtypes based on the predominant bowel habits as determined by the Bristol Stool Form Scale (BSFS). The subtypes are:
01:20Drugs Affecting GI Tract Motility: Adsorbents as Antidiarrheal Agents
Adsorbents...