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.
Silencing Visceral Nociceptors By Targeting NaV1.1: A Novel Therapeutic Approach For Treating Irritable Bowel Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$696,809.00
Summary
Patients with Irritable Bowel Syndrome suffer from chronic abdominal pain and co-morbidities such as over-active bladder. These symptoms arise from sensory nerve fibres in the colon and bladder that signal pain to innocuous stimuli. We are excited to report that a specific voltage-gated sodium channel, called NaV1.1, plays a key pathological role in generating these symptoms. Here, we will specifically target and block NaV1.1 expressing pain-sensing neurons, provide key advances for therapies.
Is Overactive Bladder A 'Bladder Itch'? Identification Of Itch Specific Pathways Within The Bladder
Funder
National Health and Medical Research Council
Funding Amount
$720,585.00
Summary
Overactive bladder is a leading cause of nocturia, urgency and incontinence. These symptoms arise from sensory nerve fibres in the bladder. We have identified key irritant mechanisms, including the bile acid receptor TGR5 and Mrgpr family, thought to only exist in the skin, also innervate the bladder. We hypothesis that the clinical entity overactive bladder, is triggered by pathological activation of bladder afferents by such irritants and that overactive bladder is essentially a bladder itch.
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.
Strategies To Restore Bladder Control After Peripheral Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$519,967.00
Summary
A major complication of pelvic surgery is loss of bladder control, mainly due to nerve injury at the time of removing cancerous tissue. This has a big effect on quality of life. Very little research has been conducted on injured bladder nerves. In this project we will investigate what happens to bladder nerves after injury and how we can make them regrow. We will also investigate if undamaged bladder nerves can be made to compensate for the lost function.
Can Persistent Bladder Pain Be Treated By Targeting TRPA1 Expressing Nociceptors?
Funder
National Health and Medical Research Council
Funding Amount
$687,730.00
Summary
Persistent visceral pain is extremely difficult to treat and manage. To solve this problem we need to understand how pain nerves in internal organs differ from those in skin and muscle. We have discovered a pain-detecting molecule TRPA1 in bladder sensory nerves. We aim to show how bladder inflammation changes the function of these bladder pain detectors and test a new way of selectively anesthetising them. We also will use a new technique to study how the bladder lining detects pain.
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.
Immune Activation In Functional Gastrointestinal Disorders
Funder
National Health and Medical Research Council
Funding Amount
$471,597.00
Summary
Up to 30% of Australians are estimated to suffer from Functional Gastrointestinal Diseases such as Irritable Bowel Syndrome and Functional Dyspepsia, but the cause of these chronic diseases is unknown. Alterations in the immune system are increasingly suggested, but little is known about how this leads to the debilitating symptoms of discomfort and pain. This project combines immunology studies with neuroscience to determine the key mediators involved and how they communicate with nerves.