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
Neurochemicals In The Control Of Human Bladder Function
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
The problem of urinary incontinence has received little attention from the medical and scientific research community until the last 10-15 years. Urinary incontinence can cause severe distress and is a taboo subject, even though it affects 30-40% of women. Public figures speak out about their experiences with breast cancer or heart disease, but not about leakage of urine. Elderly people with incontinence are forced into nursing homes, with major costs to the community. Incontinence is a major cli ....The problem of urinary incontinence has received little attention from the medical and scientific research community until the last 10-15 years. Urinary incontinence can cause severe distress and is a taboo subject, even though it affects 30-40% of women. Public figures speak out about their experiences with breast cancer or heart disease, but not about leakage of urine. Elderly people with incontinence are forced into nursing homes, with major costs to the community. Incontinence is a major clinical problem: although over 800 new patients per annum are seen at our Pelvic Floor Unit, the waiting time for a first appointment is 14-15 weeks. There are four main types of urine leakage: - stress incontinence (weak pelvic floor muscles); - overflow incontinence (seen in men with prostatic hypertrophy); - sensory urgency (frequent, uncomfortable desire to urinate); and - detrusor instability (bladder muscle spasms with leakage). We are primarily interested in detrusor instability and sensory urgency, which cause 35% of incontinence in general, but up to 85% of cases in the elderly. Patients suffer from an urgent desire to visit the toilet frequently, and may leak urine if they cannot reach the toilet quickly. Unlike stress incontinence, it cannot be corrected by pelvic floor surgery. Drug treatment is often unsuccessful, with many unacceptable side effects. In our research group, we have found that the sensory nerve which convey the sensation of bladder fullness, are overabundant and display increased amounts of neurochemicals. Our studies in isolated bladder muscle from these patients have shown abnormalities in responsiveness. Thus bladder from women with urge incontinence is resistant to drugs which abolish contraction in normal bladder. In this project we plan to find out why such changes occur. We will use new techniques to study bladder nerves and the receptors which convey the message to contract the bladder muscle.Read moreRead less
Non-neuronal ATP: Regulation Of Release And Action In The Bladder
Funder
National Health and Medical Research Council
Funding Amount
$451,553.00
Summary
Incontinence disorders are costly and debilitating. How the bladder signals the normal sensation of fullness as well as the urgent need to void urine (urgency) is still not fully understood. The signaling molecule ATP is released during bladder stretch. Using animal and human bladder, we will study how the bladder lining is involved in this signaling process, by measuring how bladder chemicals interact with stretch to modulate ATP release, and how ATP can influence nerve impulses to the brain.