# Role for protease activity in visceral pain in irritable bowel syndrome



## eric (Jul 8, 1999)

Public release date: 15-Feb-2007 Journal of Clinical Investigation Proteases cause pain in irritable bowel syndromeIrritable bowel syndrome (IBS) is a common gastrointestinal disorder in the developed world. It is characterized by altered bowel function, abdominal discomfort, and pain. However, there are few effective treatments for IBS, in part because the molecular mechanisms underlying the disease symptoms have not been well defined. But now, researchers from the University of Calgary have provided evidence that serine proteases and PAR2 might provide new therapeutic targets for the treatment of IBS.In the study, which appears online on February 15 in advance of publication in the March print issue of the Journal of Clinical Investigation, Nathalie Vergnolle and colleagues show that colonic biopsies from individuals with IBS release increased amounts of serine proteases when cultured in vitro, compared with colonic biopsies from healthy individuals. Likewise, colonic washes from individuals with IBS contained higher levels of serine proteases than did colonic washes from healthy individuals. The supernatant from cultured colonic biopsies from individuals with IBS activated mouse sensory neurons in vitro and caused mice to exhibit increased responsiveness to pain when it was administered into the colon. Both these effects were dependent on serine proteases in the supernatant and were mediated by activation of a protein known as PAR2, leading the authors to suggest that targeting serine proteases and/or PAR2 might provide sufferers of IBS with relief from their intense abdominal pain.###TITLE: Role for protease activity in visceral pain in irritable bowel syndromeView the PDF of this article at: https://www.the-jci.org/article.php?id=29255


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## eric (Jul 8, 1999)

FYIProteases Cause Pain In Irritable Bowel Syndromehttp://www.sciencedaily.com:80/releases/20...70215181503.htm


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## 17014 (Apr 13, 2005)

There seems to go on a lot of research for visceral pain in IBS. Good to know, they don`t ignore this pain issue and do something, and hopefuly bring a working IBS drug on the market (someday). But I`m a bit confused with these studies. What the heck is the cause of visceral IBS pain? I`ve read a lot diffrent studies. In the early days they talk about Serotonin is the cause of pain. Then substance P is to high. Then Melatonin. Now serine proteases. What`s next?


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## SpAsMaN* (May 11, 2002)

Sensitivity may play a major role in IBS.Perhaps creating chaotic contractions/spasms.


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## eric (Jul 8, 1999)

Spasman, your friend Barbra G was involved in this study.







Serotonin is still important in IBS as are mast cells and ec cells.The digestive system is so complex, some things maybe a cascade or domino effect. There is also a lot to research and figure out when it comes to how it all works and the communication between digestion and the brain and back.serine proteases for digestion are released I believe from the pancreas. This is interesting research. Onething is to be careful of wording. IT says causes pain, but not sure it is "THE" cause of pain. Maybe another target in a long list.


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## 17014 (Apr 13, 2005)

What`s the benefit of these studies?


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## eric (Jul 8, 1999)

IBS is Incompletely understood, but not totally however. There are things they know.So the benefit is to figure systems out and to see what actually does what and causes what.


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## 17014 (Apr 13, 2005)

> quote:So the benefit is to figure systems out and to see what actually does what and causes what.


Why the heck are there 10000000000000 studies for IBS and not ONE working drug.


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## eric (Jul 8, 1999)

Some drugs work for some people already.An itergrated approach to IBS helps most IBSers and targetsd more global symptoms then just one or two symptoms. There is also mild moderate and severe IBS and people may require different approaches based on being mild moderate or severe. Until they figure somethings out fully, then they can't really create a drug on a guess.The new CRF drugs maybe promosing as well, but others are in the pipeline.Two people can have the exact same problem, but do to their genetic makeup, their environmental makeup and who they are, present differently with symptoms. That is why its important to treat the whole person.


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## eric (Jul 8, 1999)

1: Clin Gastroenterol Hepatol. 2007 Mar 1; [Epub ahead of print] Links A Pilot Study of Fecal Serine-Protease Activity: A Pathophysiologic Factor in Diarrhea-Predominant Irritable Bowel Syndrome.Roka R, Rosztoczy A, Leveque M, Izbeki F, Nagy F, Molnar T, Lonovics J, Garcia-Villar R, Fioramonti J, Wittmann T, Bueno L. Institut National de la Recherche Agronomique, Neuro-Gastroenterology & Nutrition Unit, Toulouse, France.BACKGROUND & AIMS: The pathogenesis of irritable bowel syndrome (IBS) remains only partially understood, and no specific or universally effective patient management procedure has been developed to date. Our study was designed to evaluate if colonic luminal serine-proteases may be a relevant pathophysiologic marker of IBS. METHODS: Fecal samples of 38 IBS patients, 15 patients with ulcerative colitis (UC), and 15 healthy controls were studied. Fecal serine-protease activity was determined photometrically by using azocasein as a proteolytic substrate; fecal pancreatic elastase-1 and mast cell tryptase content were measured by enzyme-linked immunosorbent assay. Fecal secretory leukocyte protease inhibitor concentration was determined by enzyme-linked immunosorbent assay in control subjects and in patients with diarrhea-predominant IBS. RESULTS: Fecal serine-protease activity was 3-fold higher in patients with diarrhea-predominant IBS than in both controls and IBS patients with either constipation or alternating bowel habits. Fecal serine-protease activity was not correlated with the frequency of bowel movements in all groups. Increased serine-protease activity also was detected in stools of UC patients. No significant difference was observed in the fecal mast cell tryptase and pancreatic elastase concentrations between all groups, or in the fecal secretory leukocyte protease inhibitor concentration between controls and diarrhea-predominant IBS patients. CONCLUSIONS: Fecal serine-protease activity is increased markedly in patients with diarrhea-predominant IBS. This increase, however, is not coupled with changes in either mast cell tryptase or pancreatic elastase concentrations. Thus, serine-protease activity in the colon may be a pathophysiologic factor in the development of diarrhea-predominant IBS.PMID: 17336590


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