Proteases Cause Pain In Irritable Bowel Syndrome

Irritable 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 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 syndrome

AUTHOR CONTACT:
Nathalie Vergnolle
University of Calgary, Calgary, Alberta, Canada.

Contact: Karen Honey
Journal of Clinical Investigation