Grant: Operating Grant

Irritable bowel syndrome (IBS) is a very common disorder for which there are currently no proven treatments. This proposal examines causes of pain in patients suffering from post-infectious IBS (IBS which onsets following an acute bacterial infection in the colon). Recent studies have shown that chronic stress is frequently associated with the development of IBS following an acute bacterial infection in the colon. Our hypothesis is that chronic stress releases mediators which in turn can signal to pain neurons innervating the gut and this greatly exacerbate the abnormal pain signalling that occurs following infection. We have developed an animal model of post-infectious IBS which allows us to examine the interaction between a previous infection and chronic stress. We have new data showing that chronic stress greatly exacerbates the pain signalling following resolution of an acute colitis and have identified several novel targets underlying these changes. We have also shown that the supernatant (fluid containing inflammatory mediators) obtained from human biopsies of the colon from post-infectious IBS sufferers can re-capitulate these findings when incubated with mouse pain neurons. The research plan is to use electrophysiological and molecular techniques to clarify the role of these new targets in animal and human models. Our ultimate goal is to identify the best targets for treating pain in this disorder and possibly new means of diagnosing this disorder.