Sensory Mechanisms In Normal Bladder And In Cystitis
Funder
National Health and Medical Research Council
Funding Amount
$408,861.00
Summary
The function of the lower urinary tract is to store urine and release it at appropriate times. This requires neural circuits in the brain, spinal cord and peripheral ganglia. When the bladder fills, sensory neurones fire and activate these neural circuits to store urine or to empty the bladder. If sensory neurones are too easily excited (a process called sensitisation ) this will lead to clinical disorders, including the common painful bladder syndromes, whose cause is not known (interstitial cy ....The function of the lower urinary tract is to store urine and release it at appropriate times. This requires neural circuits in the brain, spinal cord and peripheral ganglia. When the bladder fills, sensory neurones fire and activate these neural circuits to store urine or to empty the bladder. If sensory neurones are too easily excited (a process called sensitisation ) this will lead to clinical disorders, including the common painful bladder syndromes, whose cause is not known (interstitial cystitis, sensory urgency etc). These are characterised by pelvic pain, urinary urgency, frequency and, in some cases, urge incontinence (loss of urine for no apparent reason) which results from unstable or overactive bladder. Despite a large database of knowledge about the sensory innervation of the bladder, many important gaps still exist. These gaps have restricted the development of new therapies. For example, we have little idea about exactly which functional classes of sensory neurones signal filling of the normal bladder or what different types of information they carry. This is vital information for understanding which neurones are affected in disease states and whether they are all affected in the same way. We have developed new methods that will allow us to identify the major classes of sensory neurones that innervate the bladder, what they respond to and how they are activated. We will also determine whether some classes are preferentially sensitised by inflammation and the most important mechanisms that are likely to underlie this. The significance of this project is that it provides the basic scientific understanding of sensory innervation of the bladder and will identify potential targets for selective pharmacological intervention in common bladder disorders.Read moreRead less
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.
Role Of Sensory Neurons In Obstruction-induced Bladder Overactivity
Funder
National Health and Medical Research Council
Funding Amount
$340,986.00
Summary
About 20% of people over the age of 40 have the clinical syndrome of an “overactive bladder”, which causes symptoms of urgency, frequency and incontinence. The mechanisms causing bladder overactivity are not known. This project will identify sensory neurons, which become overexcited, and determine which mediators and ionic channels are responsible for this. Our new data will identify selective pharmacological targets for new therapies and diagnostic tools for these distressing bladder disorders.
Nanoengineered Bioelectronic Systems For All-Optical Control Of Neuron Growth And Stimulation
Funder
National Health and Medical Research Council
Funding Amount
$757,452.00
Summary
Nerve cells are the primary signal carriers of the human body. When they cease to function normally, our bodies ability to function and sense the physical world is influenced catastrophically. We will develop a new bioelectronic system made by printing clever inks that can artificially stimulate nerve cells without the typical requirements for invasive metal electrodes or external power. These new scientific advances will revolutionize nerve cell repair and treatment of neurological disorders.
Plasticity And Regeneration Of Bladder Motor Nerve Circuits After Injury
Funder
National Health and Medical Research Council
Funding Amount
$333,313.00
Summary
Our goal is to determine ways of improving the recovery of bladder-controlling nerves after they are injured, which has devastating effects on bladder function. This can happen because of lumbosacral spinal nerve damage or pelvic surgery. We also expect to establish broad principles that may be tested in other neurological conditions that affect bladder function, such as neurodegenerative disorders (e.g. diabetes) and spinal cord injury.
How Intestinal Motility Activates Sensory Pathways
Funder
National Health and Medical Research Council
Funding Amount
$555,875.00
Summary
Pain and discomfort from the gut are common and unpleasant. We understand how gut sensory nerve cells work, at the cellular, molecular and genetic level. However, movement of the gut wall and contents are the major cause of activation of sensory neurons. We know little about which particular patterns of movement cause pain. This is crucial information for accurately diagnosing human gut disorders, for monitoring effectiveness of treatments and for identifying potential new drug targets.