Sacral Parasympathetic Innervation Of Distal Bowel
Funder
National Health and Medical Research Council
Funding Amount
$314,983.00
Summary
Not a topic for polite conversation, normal movements of the colon and rectum are essential for good health and a sense of wellbeing. Constipation, diarrhoea, incontinence and pain result from disordered motility. One major control mechanism is the parasympathetic innervation. While we know of its importance, how it works in health and diseases is poorly understood. This project will use state-of-the-art techniques to study this pathway in order to understand its role in health and disease
Currents That Set The Excitability Of Enteric Neurons And Their Roles At Cell And Organ Levels
Funder
National Health and Medical Research Council
Funding Amount
$459,014.00
Summary
The intestine is subject to a number of disorders of its normal control by nerves, including diarrhoea, constipation and slow transit disorders. Chronic and debilitating derangement of intestinal function occurs in irritable bowel syndrome, which affects around 10-15% of people in our community, about 1% at any one time. Irritable bowel syndrome can persist for many years, and there is no adequate therapy. For some patients no medication gives relief, and for most the relief is minimal. The refl ....The intestine is subject to a number of disorders of its normal control by nerves, including diarrhoea, constipation and slow transit disorders. Chronic and debilitating derangement of intestinal function occurs in irritable bowel syndrome, which affects around 10-15% of people in our community, about 1% at any one time. Irritable bowel syndrome can persist for many years, and there is no adequate therapy. For some patients no medication gives relief, and for most the relief is minimal. The reflexes in the intestine that control its movements and secretion depend for their initiation on a special type of neuron, known as the intrinsic primary afferent neuron. These neurons have properties that determine how active they are. These properties distinguish them from all other enteric neurons. If the activity of intrinsic primary afferent neurons is controlled, then the intensity and character of enteric reflexes are also controlled. Thus it is feasible to target molecules in these neurons that could be used to treat constipation or diarrhoea, or to accelerate movement of food along the intestine. Our work has identified molecular targets and some of the medicinal compounds that could be useful to patients. The project will further define the molecular targets, determine the specificity of potential treatments and test the effectiveness of the medicinal compounds in an animal model.Read moreRead less
The Mechanisms Through Which Opiates Cause Gastrointestinal Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$410,594.00
Summary
Opiates are the mainstay analgesics for severe pain. However, their use in pain relief can be greatly limited due to gut-related side-effects. These include chronic constipation, which is mediated through actions on neurons in the intestine. In this proposal we will examine the role of key proteins, known as beta arrestins, in the generation of opiate-induced constipation. Knowledge derived from this study will facilitate the development of analgesics with fewer gastrointestinal side-effects.