Grant: Operating Grant

In Canada, at least 2 million people suffer from some form of disorder of gastrointestinal motility. This is causing these patients to assess their quality of life as severely impaired. It also costs the health care system between $370 million and $1 billion per year. The indirect costs such as staying home from work are even higher. Although the need for treatment is high, there are few options and some good drugs such as cisapride and tegaserod have been taken off the market. This has also led to the pharmaceutical industry withdrawing research support. Hence it is critical that research is conducted into the causes of gastrointestinal motor abnormalities and it is critical that we find new targets for pharmaceutical intervention. The health care costs are driven by frustration of patients related to the limited availability of treatment. And this is based on our limited understanding of the underlying pathophysiology, which we will address in this application. We will investigate new hypotheses related to the mechanisms behind peristalsis and segmentation, the major motor activities of the stomach and small intestine. We are proposing that the study of the role of interstitial cells of Cajal (the pacemaker cells of the gut) is a very promising avenue for understanding of motor control and motor abnormalities. We will study the electrophysiological basis of pacemaker activity using the most advanced electrophysiological techniques in combination with calcium imaging. We will investigate comprehensive and unique hypotheses related to the mechanism behind segmentation. We will study how these control systems are affected by inflammation and we will investigate our hypotheses in humans in collaboration with clinical investigators at McMaster University.