2. Academic Validation
  3. Lidocaine ameliorates intestinal barrier dysfunction in irritable bowel syndrome by modulating corticotropin-releasing hormone receptor 2

Lidocaine ameliorates intestinal barrier dysfunction in irritable bowel syndrome by modulating corticotropin-releasing hormone receptor 2

  • Neurogastroenterol Motil. 2023 Sep 21;e14677. doi: 10.1111/nmo.14677.
Yanrong Wang 1,  Mingbiao Qiao 2,  Xue Yao 3,  Zhonghui Feng 4,  Ruiqi Hu 5,  Jianguo Chen 5,  Lei Liu 3,  Jinbo Liu 5,  Yueshan Sun 3,  Yuanbiao Guo 3
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Sichuan Tianfu New Area People's Hospital, Chengdu, China.
  • 2 Department of Pathology, De Yang People's Hospital, Deyang, China.
  • 3 Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, The Second Chengdu Hospital Affiliated to Chongqing Medical University, Chengdu, China.
  • 4 Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, The Second Chengdu Hospital Affiliated to Chongqing Medical University, Chengdu, China.
  • 5 Department of Clinical Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
PMID: 37736684 DOI: 10.1111/nmo.14677
Abstract

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.

Keywords

corticotropin-releasing hormone receptor 2; intestinal barrier; lidocaine; stress; tight junctions.

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