Neuroimmune Interactions In Functional And Organic Gastrointestinal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are chronic, incurable diseases of the lower gastrointestinal tract with unknown causes and poor treatment options. Both the immune and nervous systems are altered in GI disease, but have traditionally been studied in isolation. My research investigates how the neuro-immune axis is altered in these diseases, using animal models and human tissue samples to identify novel treatment options for these debilitating diseases.
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.
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
Is Abdominal Discomfort A “colonic Itch”? Identification Of Itch Specific Pathways In The Gut In Health And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$906,996.00
Summary
Chronic abdominal pain is a major worldwide problem. TGR5 and Mrgpr receptors are expressed by neuronal pathways innervating the skin, where they detect irritants and transmit itch. Our novel, innovative project shows a similar pathway exists within the viscera, which plays a major and unappreciated role in chronic abdominal pain. These receptors represent novel targets for therapeutic treatment, potentially creating multibillion-dollar savings to the Australian economy and healthcare systems.
GABA(B) Receptor Modulation Of Gastrointestinal Function In Health And Disease By Alpha-Conotoxins
Funder
National Health and Medical Research Council
Funding Amount
$689,050.00
Summary
Chronic visceral pain is a common and debilitating condition arising from numerous diseases that affect our internal organs. There is a desperate need for more information about the mechanisms responsible for signalling chronic visceral pain to provide therapies and potentially find a cure for it. Our research focuses on ?-conotoxins (small peptides from marine cone snail venom) as novel potential therapeutic agents for the treatment of chronic visceral 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
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.
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.
Chronic inflammation underlies common and debilitating diseases and causes pain by unknown mechanisms. There is an urgent need to gain a deeper understanding of the mechanisms of chronic pain, which will allow the development of improved therapies with fewer side-effects. Our research program investigates the mechanisms of pain that are associated with inflammatory bowel disease and irritable bowel syndrome, with the goal of developing more effective and selective therapies.