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
We use a mouse model of inflammatory bowel disease (IBD) to determine how sensations from the inflamed gut are processed in the spinal cord. Over 60,000 Australians suffer from IBD and debilitating pain is a major symptom. Surprisingly, we know very little about how pain signals originating in the normal or the diseased gut are organised and processed in the central nervous system. Obtaining such information is a necessary first step before we can develop therapies to relieve gut pain.
A Novel Technique For Prolonged Silencing Of Visceral Pain Without Opiates
Funder
National Health and Medical Research Council
Funding Amount
$637,383.00
Summary
There has been substantial interest in the community for pain relief without opiates. This project demonstrates a new strategy to suppress pain at the source for prolonged periods, by suppressing activity in the sensory nerve endings that detect pain, not by acting in central pathways like opiates. To do this, we use a harmless virus to shut down a vital sodium channel for pain perception. These experiments use techniques that were recently developed in our lab and cant be performed elsewhere.
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.
The human brain has many subdivisions (�areas�) that are dedicated to vision, but in many cases their functions remain unclear. This project will study an area located deep in the brain, about which very little is known, and which appears to be affected from early stages in conditions such as Alzheimer�s disease. By understanding the patterns of electrical activity of cells in this region, and their connections with other brain areas, we hope to decipher their contribution to sensory cognition.
Rapid Plasticity In Sensory Systems - Linking Neuronal Adaptation And Perception
Funder
National Health and Medical Research Council
Funding Amount
$650,810.00
Summary
The activity of individual sensory neurons in the brain is surprisingly variable and continuously changing. It is unclear how reliable perception of the world can be generated from the activity of “noisy” neurons, and it remains unclear why neuronal sensitivity should change in the first place! This project will give insights into how groups of sensory neurons collectively overcome their intrinsic variability to support reliable visual perception.
Context Is Everything – Understanding How Spatial, Temporal And Behavioural Context Affect Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$512,382.00
Summary
A possum in a tree is cute to see on a bushwalk, but scary to hear when we are trying to sleep. This illustrates that how we perceive a “target” is affected by “modulators” that are close in space or time to the target, or by the task at hand. Deficits in contextual modulation are apparent in many neurological conditions. This project will investigate the neural circuitry that mediates spatial, temporal and task-related contextual modulation.
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.
Cortical Excitation In Migraine: Using Vision To Understand And Track Brain Excitability
Funder
National Health and Medical Research Council
Funding Amount
$521,628.00
Summary
Migraine is a common neurological condition affecting approximately 15% of adults. Therapies are most effective if used early, yet many people are unable to predict their migraines or to recognize early signs. In addition to headache, key symptoms include abnormal visual and auditory experience. We propose that aspects of vision and hearing will vary systematically according to the current brain status. Our translational goal is to develop tests that allow individuals to better manage migraine.
Discovery Early Career Researcher Award - Grant ID: DE180100433
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Cortical layer specific functional imaging of the human brain. This project aims to record layer specific cortical activity in humans by leveraging ultra-high field magnetic resonance imaging. It expects to yield robust techniques for the general analysis of neuroimaging-based, layer-specific measurements. This project will progress the fields of cognitive neuroscience and neuroimaging as well as bring the field of neuroimaging closer to that of neurophysiology and thus facilitate collaboration ....Cortical layer specific functional imaging of the human brain. This project aims to record layer specific cortical activity in humans by leveraging ultra-high field magnetic resonance imaging. It expects to yield robust techniques for the general analysis of neuroimaging-based, layer-specific measurements. This project will progress the fields of cognitive neuroscience and neuroimaging as well as bring the field of neuroimaging closer to that of neurophysiology and thus facilitate collaboration among researchers.Read moreRead less