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Cited by 112Gastrointestinal motility and disordersInflammatory Bowel DiseasePain Mechanisms and Treatments

Fecal proteases from diarrheic-IBS and ulcerative colitis patients exert opposite effect on visceral sensitivity in mice

Annaházi, Anita, Gecse, Krisztina, Dabek, Marta, Ait-Belgnaoui, Afifa, Rosztóczy, András, Róka, Richárd, Molnár, Tamás, Theodorou, Vassilia +3 more·2009·Pain
DOI 10.1016/j.pain.2009.04.017
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Abstract

Elevated colonic luminal serine-protease (Ser-P) activity of diarrhea-predominant IBS (IBS-D) patients evokes a proteinase-activated receptor (PAR)-2-mediated colonic hypersensitivity in mice. Despite similarly elevated Ser-P levels in feces, patients with IBD exhibit visceral hypo- or normosensitivity to rectal distension, as opposed to IBS-D. To explain these discrepancies we studied the effect of colonic infusion of fecal supernatants from ulcerative colitis (UC) patients to colorectal mechanical sensitivity of mice and explored the involvement of PAR-4 and its activator Cathepsin-G (Cat-G). Fecal protease activities were assayed in healthy subjects, IBS-D and UC patients in presence or not of antiproteases or Cat-G inhibitor. Following intracolonic infusion of fecal supernatants from healthy subjects, IBS-D and UC patients or PAR-4 activating peptide (PAR-4-AP) or Cat-G, EMG response to colorectal balloon distension was recorded in mice. This nociceptive response was also determined after treatment with pepducin (PAR-4 antagonist) on UC supernatant or after a preincubation with antiproteases or Cat-G inhibitor. In contrast to IBS-D supernatant, UC supernatant promoted colonic hyposensitivity to distension, an effect mimicked by PAR-4-AP or Cat-G. UC supernatant-induced hypoalgesia was inhibited by a cocktail of antiproteases. However, blockade of PAR-4 or Cat-G inhibition resulted in colonic hypersensitivity similar to that observed after IBS-D supernatant infusion. Despite similarly elevated Ser-P activities, IBS-D and UC fecal supernatant display visceral pro- and antinociceptive effects in mice, respectively. Visceral hyposensitivity induced by fecal supernatant from UC patients results from PAR-4 activation by cathepsin-G, counterbalancing the pronociceptive effect of simultaneous PAR-2 activation.

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Crossref · 10.1016/j.pain.2009.04.017

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  • Intracolonic administration of fecal supernatants from IBS-D and IBS-C patients increased the visceromotor response to distension, with evidence of both allodynia and hyperalgesia.

    “Intracolonic administration of fecal supernatants from IBS-D and IBS-C patients increased the visceromotor response to distension, with evidence of both allodynia and hyperalgesia.159,160”

    From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [159]

  • Fecal supernatants from UC patients had the opposite effect, decreasing the visceromotor response in a PAR-4-dependent manner.

    “In contrast, fecal supernatants from UC patients had the opposite effect, decreasing the visceromotor response in a PAR-4-dependent manner.159”

    From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [159]

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Authors
Annaházi, A., Gecse, K., Dabek, M., Ait-Belgnaoui, A., Rosztóczy, A., Róka, R., Molnár, T., Theodorou, V., Wittmann, T., Bueno, L., & Eutamene, H.
Affiliations
  • Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
  • University of Szeged (HU)
ORCID
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2009-07
Volume
144
Issue
1
Pages
209-217
ISSN
0304-3959 (ISSN-L)
DOI
10.1016/j.pain.2009.04.017
OpenAlex
W1973233423
Cited by
112
References
37
Citations by year
2026: 2 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 8 · 2021: 11 · 2020: 3 · 2019: 7 · 2018: 6 · 2017: 5 · 2016: 11 · 2015: 6 · 2014: 7 · 2013: 8 · 2012: 7
FWCI
7.79
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
Funders
Institut National de la Recherche Agronomique
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
diarrhea-predominant irritable bowel syndrome, ulcerative colitis, visceral sensitivity, colonic hypersensitivity, proteinase-activated receptor 4, protease-activated receptor 2, cathepsin G, serine protease, colorectal distension, fecal supernatants, pepducins, inflammatory bowel disease
MeSH terms
Adult, Analysis of Variance, Animals, Colitis, Ulcerative, Enzyme Inhibitors, Feces, Female, Humans, Male, Mice, Inbred C57BL, Middle Aged, Perception, Sensory Thresholds, Serine Endopeptidases, Viscera, Irritable Bowel Syndrome, Receptors, Proteinase-Activated, Mice

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