Abstract

Background and Aims: Crohn’s Disease (CD), a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn’s ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS)-induced ileitis rats.Methods: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48), an equal volume of 30% Ethanol (n = 24), and Saline (n = 24), respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR) to 20, 40, 60, 80, and 100 mmHg colorectal distension pressure (CRD) at day 1, 3, 7, 14, 21, and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1β, IL-6), and dorsal root ganglia (T11) for determination of calcitonin gene-related peptide by immunohistochemistry, respectively.Results: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05) VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05) in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats.Conclusion: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral hypersensitivity, as well as for establishing the therapeutic protocol for Crohn’s ileitis.

Highlights

  • Crohn’s disease, a major form of human inflammatory bowel disease (IBD), is a chronic, remitting, and relapsing inflammatory disorder of gastrointestinal tract that can affect animal and almost all ages of human population

  • Crohn’s disease, a major form of human IBDs, is a chronic, remitting, and relapsing inflammatory disorder of gastrointestinal tract that can affect animal and almost all ages of human population. It leads to a wide range of symptoms, such as diarrhea, nausea, abdominal pain, and visceral hypersensitivity (VH), which has a significant effect on the life quality of affected patients (Wagtmans et al, 1998; Simren et al, 2002; Faure and Giguere, 2008)

  • The colitis could not be appropriate for studying the precise mechanism of VH accompanying Crohn’s disease (CD) because its location, duration, microbiota and central regulating mechanism are different from the CD of ileal origin

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Summary

Introduction

Crohn’s disease, a major form of human IBDs, is a chronic, remitting, and relapsing inflammatory disorder of gastrointestinal tract that can affect animal and almost all ages of human population. It leads to a wide range of symptoms, such as diarrhea, nausea, abdominal pain, and VH, which has a significant effect on the life quality of affected patients (Wagtmans et al, 1998; Simren et al, 2002; Faure and Giguere, 2008). The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS)-induced ileitis rats

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Conclusion

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