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Cited by 526Gastrointestinal motility and disordersIon Channels and ReceptorsPain Mechanisms and Treatments

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

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Akbar, A, Yiangou, Y, Facer, P, Walters, J R F, Anand, P, Ghosh, S·2008·Gut
DOI 10.1136/gut.2007.138982PMC PMC2564830
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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.

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Crossref · 10.1136/gut.2007.138982

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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 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.CC BY · PubMed Central
Figure 2 Transient receptor potential vanilloid type-1 (TRPV1) levels for the irritable bowel syndrome (IBS) and control groups; p<0.001.
Figure 2 Transient receptor potential vanilloid type-1 (TRPV1) levels for the irritable bowel syndrome (IBS) and control groups; p<0.001.CC BY · PubMed Central
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 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.CC BY · PubMed Central
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<0.001. Spearman correlation r = 0.45, p = 0.02. (B) Scatter plot to show the correlation between TRPV1 levels and average pain scores (VASav) in control subjects. Pearson correlation r = −0.1, p = 0.34. (C) Scatter plot to show the correlation between TRPV1 levels and VASav in all subjects (controls and IBS). Pearson correlation r = 0.6, p<0.001. Spearman correlation r = 0.46; p<0.001.
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<0.001. Spearman correlation r = 0.45, p = 0.02. (B) Scatter plot to show the correlation between TRPV1 levels and average pain scores (VASav) in control subjects. Pearson correlation r = −0.1, p = 0.34. (C) Scatter plot to show the correlation between TRPV1 levels and VASav in all subjects (controls and IBS). Pearson correlation r = 0.6, p<0.001. Spearman correlation r = 0.46; p<0.001.CC BY · PubMed Central

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Metadata

Authors
Akbar, A., Yiangou, Y., Facer, P., Walters, J. R. F., Anand, P., & Ghosh, S.
Affiliations
  • Imperial College London (GB)
  • Hammersmith Hospital (GB)
Corresponding author
Ghosh, S
ORCID
Venue
Gut
Publisher
BMJ
Published
2008-02-27
Volume
57
Issue
7
Pages
923-929
ISSN
0017-5749 (ISSN-L)
DOI
10.1136/gut.2007.138982
PMC
PMC2564830
OpenAlex
W2165979101
Cited by
526
References
49
Citations by year
2026: 19 · 2025: 16 · 2024: 34 · 2023: 25 · 2022: 21 · 2021: 36 · 2020: 28 · 2019: 27 · 2018: 30 · 2017: 30 · 2016: 41 · 2015: 25 · 2014: 36 · 2013: 39 · 2012: 26
FWCI
29.02
Type
journal article
Language
en
Open access
Locations
  • Gut (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion)
Funders
  • GlaxoSmithKline
  • London School of Hygiene and Tropical Medicine
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Keywords
irritable bowel syndrome, TRPV1, capsaicin receptor, visceral pain, visceral hypersensitivity, abdominal pain, sensory nerve fibers, substance P, mast cells, lymphocytes, colonic mucosa, low-grade inflammation
MeSH terms
Adult, Aged, Anxiety, Depression, Female, Humans, Immunoenzyme Techniques, Intestinal Mucosa, Male, Middle Aged, Nerve Fibers, Neurons, Afferent, Pain Measurement, Abdominal Pain, Inflammation Mediators, Irritable Bowel Syndrome, TRPV Cation Channels

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