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.
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.
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.
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
Ion Channels Underlying Inflammatory And Post-inflammatory Visceral Mechanical Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$453,439.00
Summary
Inflammation causes tissue damage that triggers ion channels within sensory nerve fibres to produce greater signals in response to mechanical events, causing acute pain. In chronic pain, although the inflamed tissue has healed, sensory nerve fibres fail to "reset" back to normal. Often chronic pain is more severe than acute pain. This project will identify which ion channels are responsible for signalling acute and chronic visceral pain, explaining why sensory nerve fibres fail to reset.
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
The Role Of Adipokines In Modulation Of Gastric Vagal Afferent Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$624,535.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals are disordered in obesity and may be influenced by factors released from fat stores in the body. The aim of this project is to determine how these factors interact with gastric nerve satiety signals and thus identify targets for the pharmacological treatment of obesity.
Target detection in visual clutter. The interdisciplinary nature of the project will offer a stimulating environment for training a postdoctoral worker in the hot topic of computational neuroscience. While computationally expensive solutions to moving target detection in clutter have been implemented using conventional engineering, this project will offer insight into the efficiency of the biological brain (with benefit of millions of years of evolution towards compact, economical and optimal so ....Target detection in visual clutter. The interdisciplinary nature of the project will offer a stimulating environment for training a postdoctoral worker in the hot topic of computational neuroscience. While computationally expensive solutions to moving target detection in clutter have been implemented using conventional engineering, this project will offer insight into the efficiency of the biological brain (with benefit of millions of years of evolution towards compact, economical and optimal solutions). The results will assist development of efficient artificial intelligence. It will also assist our ongoing collaborations with defence partners to develop and apply algorithms in artificial vision systems. Read moreRead less
Establishing The Physiological And Sleep Disruption Characteristics Of Wind Farm Versus Traffic Noise Disturbances In Sleep
Funder
National Health and Medical Research Council
Funding Amount
$1,357,652.00
Summary
Good sleep is essential for normal daytime functioning and health. Wind farm noise includes audible and unusually low frequency sound components, including infrasound, that could potentially disturb sleep through chronic sleep disruption and/or insomnia. This project will, for the first time, directly evaluate the sleep and physiological disturbance characteristics of wind farm noise compared to traffic noise reproduced in a specialised and carefully controlled laboratory environment.