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

A Akbar, Y Yiangou, P Facer, J R F Walters, P Anand, S Ghosh, A Akbar, Y Yiangou, P Facer, J R F Walters, P Anand, S Ghosh

Abstract

Objective: The capsaicin receptor TRPV1 (transient receptor potential vanilloid type-1) 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. TRPV1-immunoreactive nerve fibres were investigated in colonic biopsies from patients with IBS, and this was related to abdominal pain.

Methods: Rectosigmoid biopsies were collected from 23 IBS patients fulfilling Rome II criteria, and from 22 controls. Abdominal pain scores were recorded using a validated questionnaire. TRPV1-, substance P- and neuronal marker protein gene product (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 (PGP9.5) (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-immuno-reactive 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.

Figures

Figure 1. Photomicrographs showing transient receptor potential…
Figure 1. Photomicrographs showing transient receptor potential vanilloid type-1 (TRPV1)- (arrowed), substance P and protein gene product (PGP) 9.5-immunoreactive fibre immunostaining in a control (A, C and E) and an irritable bowel syndrome rectosigmoid biopsy (B, D and F), magnification ×40.
Figure 2. Transient receptor potential vanilloid type-1…
Figure 2. Transient receptor potential vanilloid type-1 (TRPV1) levels for the irritable bowel syndrome (IBS) and control groups; p
Figure 3. Photomicrographs showing CD3- and c-kit-immunoreactive…
Figure 3. Photomicrographs showing CD3- and c-kit-immunoreactive staining cells in a control (A and C, respectively) and an irritable bowel syndrome rectosigmoid biopsy (B and D, respectively). Magnification ×40.
Figure 4. (A) Scatter plot to show…
Figure 4. (A) Scatter plot to show the correlation between transient receptor potential vanilloid type-1 (TRPV1) levels and average pain scores (VASav) in irritable bowel syndrome (IBS) subjects. Pearson correlation r = 0.68, p

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