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The most recent version of this article was published on 1 July 2008

Gut. Published Online First: 5 February 2008. doi:10.1136/gut.2007.138982
Copyright © 2008 BMJ Publishing Group Ltd & British Society of Gastroenterology.

Paper

Increased capsaicin receptor TRPV1 expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain

Ayesha Akbar 1, Yiangos Yiangou 1, Paul Facer 1, Julian R F Walters 1, Praveen Anand 1 and Subrata Ghosh 1*

1 Imperial College London, United Kingdom

* To whom correspondence should be addressed. E-mail: s.ghosh{at}imperial.ac.uk.

Accepted 22 January 2008


Abstract

Objective: The capsaicin receptor TRPV1 may play an important role in visceral pain and hypersensitivity states. In irritable bowel syndrome (IBS), abdominal pain is a common and distressing symptom where the pathophysiology is still not clearly defined. We investigated TRPV1-immunoreactive nerve fibers in colonic biopsies from patients with IBS, and related this to abdominal pain.

Design, setting and patients: Recto-sigmoid biopsies were collected from 23 IBS patients fulfilling Rome II criteria, and from 22 controls. Abdominal pain scores were recorded using a validated questionnaire.

Main outcome measures: TRPV1-, substance P-, and neuronal marker PGP 9.5-expressing nerve fibres, mast cells (c-kit), and lymphocytes (CD3 and CD4) were quantified, following immunohistochemistry with specific antibodies. The biopsy findings were related to the abdominal pain scores.

Results: A significant 3.5-fold increase in median numbers of TRPV1-immunoreactive fibres was found in biopsies from IBS patients compared with controls (p< 0.0001). Substance P-immunoreactive fibres (p=0.01), total nerve fibres (PGP 9.5) (p=0.002), mast cells (c-kit) (p=0.02) and lymphocytes (CD3) (p=0.03) were also significantly increased in the IBS group. In multivariate regression analysis, only TRPV1-immunoreactive fibres (p=0.005) and mast cells (p=0.008) were significantly related to the abdominal pain score.

Conclusions: Increased TRPV1 nerve fibres are observed in IBS, together with a low-grade inflammatory response. The increased TRPV1 nerve fibres may contribute to visceral hypersensitivity and pain in IBS, and provide a novel therapeutic target.

Keywords: Irritable bowel syndrome, Mast cells, Pain, Transient receptor potential vanilloid-1 (TRPV1)


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