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.
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
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.
Mechanisms Of Activation Of Vascular Afferent Nociceptors To The Gut
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
We have recently identified the nerve fibres responsible for detecting pain from the gut. In this project we will study exactly how these nerve cells are activated by movements of the gut wall, by changes in blood vessel diameter and how this can be studied most efficiently We will use this information to develop simple preparations in which to study these sensory nerves in animal and adult tissue to test which drugs may affect their excitability and hence be useful in treating gut pain.
InTOUCH: Tactile Assessment In Children With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$176,571.00
Summary
Recent research finds that over 70% of children with unilateral cerebral palsy have impairments in touch function that affect how well they can use their hands. Until now, the severity and extent of this deficit has been unknown, and so children with cerebral palsy have not been receiving touch assessments. This project aims to increase awareness of touch impairments and achieve integration of touch assessment into routine examaination.
The broad aim of this project is to understand how the eye receives visual signals and sends them to the brain. Our experimental goal is to study the structure of neural connections in a poorly understood division of the visual system, called the koniocellular pathway. The cells of the koniocellular pathway make up close to 10 percent of all projections from the eye to the brain, but their functions are almost completely unknown. The fovea is a specialised region of the retina (the nerve cells w ....The broad aim of this project is to understand how the eye receives visual signals and sends them to the brain. Our experimental goal is to study the structure of neural connections in a poorly understood division of the visual system, called the koniocellular pathway. The cells of the koniocellular pathway make up close to 10 percent of all projections from the eye to the brain, but their functions are almost completely unknown. The fovea is a specialised region of the retina (the nerve cells which line the back of the eye). It is characterised by a very high density of cone photoreceptors, and is essential for high-acuity vision. This makes the fovea the most important part of the primate retina, but the high density of nerve cells there is thought to be the reason why the fovea is especially vulnerable to disease and age-related degeneration. Our aim is to analyse, using high-resolution microscopic techniques, the connections of koniocellular-pathway cells within the retina. We specifically aim to discover whether the koniocellular pathway contributes to foveal vision. Recent work from our and other laboratories has shown that many koniocellular-pathway cells receive functional connections from short-wavelength sensitive (blue) cone photoreceptors. Thus, our study will provide new insights into the connectivity of blue-cone pathways in the fovea. Although these experiments address basic scientific questions, they can lead to improved clinical practice. Understanding the wiring diagram of the retina can inform clinical studies of conditions such as glaucoma, and helps to give a rational basis for development of treatments. For example, dysfunction in blue-cone pathways is an early sign of glaucoma, so understanding the connections of blue-cone pathways in the fovea can lead to improved methods for early detection of this leading cause of blindness.Read moreRead less
Determining The Mechanisms Underlying Chronic Visceral Pain And Providing Novel Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Gastroenteritis activates special types of nerve endings in the gut to cause acute pain. In chronic gut pain, although the damaged tissue has healed, the nerve endings remain active and don’t reset back to normal. This project will identify why this occurs, determining pain mechanisms associated with Irritable Bowel Syndrome, a leading form of chronic pain. It will identify which ion channels and receptors can be targeted allowing the development of novel and effective therapies for pain relief.
Generation Of Complex Responses In Retinal Ganglion Cells
Funder
National Health and Medical Research Council
Funding Amount
$490,500.00
Summary
The retinal ganglion cells, whose axons form the optic nerve, comprise numerous distinct types, which respond to visual stimuli in either a simple or complex manner. The project will investigate how the complex responses of the direction-selective ganglion cells (DSGCs) and the local-edge-detector ganglion cells (LEDs) are generated. It appears that the retinal neurons providing inhibitory input to DSGCs and LEDs use different neurotransmitters, and the project will investigate how this shapes t ....The retinal ganglion cells, whose axons form the optic nerve, comprise numerous distinct types, which respond to visual stimuli in either a simple or complex manner. The project will investigate how the complex responses of the direction-selective ganglion cells (DSGCs) and the local-edge-detector ganglion cells (LEDs) are generated. It appears that the retinal neurons providing inhibitory input to DSGCs and LEDs use different neurotransmitters, and the project will investigate how this shapes the response properties of the ganglion cells. This will be done both by recording the visually evoked responses of the ganglion cells in an isolated preparation of the retina and by using two-photon laser-scanning microscopy to functionally image the neuronal interactions between the neurons that inhibit the DSGCs.Read moreRead less
The retina lines the back of the eye and sends multiple movies of the visual world to the brain. This project aims to investigate how these multiple information channels are created. Descriptions of the basic pattern of wiring in the healthy retina will help clinical researchers to understand the disruptions that occur in visual disease. The precision of normal retinal wiring also delineates the precision required to restore normal function to a diseased or degenerating eye.