Stimulant laxatives are widely used and usually very effective in the short term, but how they work is very poorly understood. Our recent work has shown that they selectively excite sensory pathways from the colon which then trigger defaecation. This points to an undiscovered mechanism that potently affects colonic sensation and motility. This is likely to be a target for new treatments for other colonic disorders such as Irritable bowel syndrome and faecal incontinence.
Interaction Of TRP Channels And Inflammatory Mediators: A Critical Role In Visceral Pain
Funder
National Health and Medical Research Council
Funding Amount
$308,747.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we feel, such as touch and pain. The function of these channels can be altered by substances released by the body during inflammation. Some TRP channels have specialized roles in signalling pain from the colon which can be enhanced during colonic inflammation. Understanding how TRP channels and inflammatory mediators function and interact is essential if we are to find treatments for colonic pain.
Identifying The Underlying Causes Of Chronic Visceral Pain And Discovering Novel Therapeutic Treatments
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Chronic pain is a major, but under appreciated social, clinical and economic challenge. Globally >1.5 billion people suffer from chronic pain. In the USA alone pain is the leading cause of disability, affecting 115 million adults and costing >$630 billion, more than cancer, heart disease and diabetes combined. By using pre-clinical models and translational science this proposal will identify the key mechanisms underlying chronic pain and also identify novel targets for new therapeutic trea ....Chronic pain is a major, but under appreciated social, clinical and economic challenge. Globally >1.5 billion people suffer from chronic pain. In the USA alone pain is the leading cause of disability, affecting 115 million adults and costing >$630 billion, more than cancer, heart disease and diabetes combined. By using pre-clinical models and translational science this proposal will identify the key mechanisms underlying chronic pain and also identify novel targets for new therapeutic treatmentRead moreRead less
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.
Understanding The Risk Factors And Burden Of Heart Disease And Stroke For Aboriginal And Torres Strait Islander Women
Funder
National Health and Medical Research Council
Funding Amount
$86,117.00
Summary
Heart disease and stroke is the leading cause of death for Aboriginal and Torres Strait Islander people, and accounts for over one quarter in the life expectancy gap. A recent survey found that 59% of Aboriginal and Torres Strait Islander women live with heart disease or stroke. This PhD seeks to understand the risks of, and hospitalisation and mortality from heart disease and stroke in Aboriginal and Torres Strait Islander women. The project is guided by a women’s Advisory Group.
Transient Receptor Potential Channels (TRPs) As Transducers And Targets In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$669,130.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we perceive, such as heat, cold, touch and pain. Some TRP channels are specialized to signal pain from visceral organs, which we must investigate if we are to find treatments for visceral pain, which are currently lacking.
How Does Inflammation Of The Gut Change Its Sensory Innervation?
Funder
National Health and Medical Research Council
Funding Amount
$613,767.00
Summary
A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for th ....A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for this type of symptom. It is becoming apparent that a large subgroup of IBS patients have undergone prior infection or inflammation, and that there are in fact changes in the types of cells in biopsies from their gut. Thus there are common features to IBS and inflammation. These may provide a means for us to find new treatments for IBS and IBD symptoms. Mice develop similar microscopic changes in the colon after experimental inflammation to those seen in humans, so we can discover more from this model. We have recently established that there are several types of sensory nerve fibres from the mouse colon and rectum that convey information about contractions, distension and chemical mediators released from tissue to the central nervous system. These are almost certainly responsible for generating symptoms in patients. We aim in this project to discover how these sensory nerves change in their responsiveness to mechanical and chemical stimuli in experimental inflammation. Importantly we shall investigate the mediators that are present in the tissue which may activate sensory nerves and-or the receptors on sensory nerves that may be increased. These experiments we hope will provide a target at which to aim novel drug treatments for symptoms of IBS and IBD.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453073
Funder
Australian Research Council
Funding Amount
$129,485.00
Summary
Establishment of a South Australian rTMS Facility. It is proposed to establish a South Australian Facility for rapid rate transcranial magnetic stimulation (TMS) which will be the only one in Australia. This Facility will provide enormous opportunities for collaborative cutting edge investigations into the role of the human cortical areas in a diverse range of tasks. For example, projects have been identified projects employing rTMS to study sensorimotor cortical plasticity, facilitate functiona ....Establishment of a South Australian rTMS Facility. It is proposed to establish a South Australian Facility for rapid rate transcranial magnetic stimulation (TMS) which will be the only one in Australia. This Facility will provide enormous opportunities for collaborative cutting edge investigations into the role of the human cortical areas in a diverse range of tasks. For example, projects have been identified projects employing rTMS to study sensorimotor cortical plasticity, facilitate functional recovery following stroke and investigate the mechanisms of savant behaviour. Provision of this Facility will provide further support for this productive and internationally renowned group of scientists to develop their research programs.Read moreRead less
How The Lateral Habenula Integrates Behavioral And Autonomic Functions: The VTA Dopamine Connection
Funder
National Health and Medical Research Council
Funding Amount
$819,904.00
Summary
When adverse events occur, the lateral habenula, an old brain nucleus, helps calculate the wisest corrective action by contributing to the “brake” that controls the brain’s dopamine reward system. Our research will show how the lateral habenula links corrective changes in behavior with coordinated changes in temperature. Understanding this link will greatly contribute to understanding the brain mechanisms that regulate our physiology during stressful situations and as part of mental illness.
Afferent stimulation-induced plasticity and its functional significance. Certain regions of the brain can reorganise (plasticity) during motor learning or when there is damage to peripheral nerves or muscles. There is a large body of evidence for these plastic changes in animals. Until recently data showing that similar changes occurred in humans was limited. However, we have recently demonstrated that certain patterns of peripheral stimulation can indeed induce similar changes in human subjects ....Afferent stimulation-induced plasticity and its functional significance. Certain regions of the brain can reorganise (plasticity) during motor learning or when there is damage to peripheral nerves or muscles. There is a large body of evidence for these plastic changes in animals. Until recently data showing that similar changes occurred in humans was limited. However, we have recently demonstrated that certain patterns of peripheral stimulation can indeed induce similar changes in human subjects. These findings are important for our understanding of the mechanisms of motor control and learning.Read moreRead less