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.