Sensory Innervation Of The Anal Region In Normal And Diabetic Guinea Pigs
Funder
National Health and Medical Research Council
Funding Amount
$372,389.00
Summary
Until something goes wrong, we take it for granted that we can empty our bowels on a regular basis, at a time and place of our choosing. Failure to achieve this is very distressing and substantially diminishes quality of life, if it occurs regularly. Disordered defecation, fecal incontinence and constipation are surprisingly common and their prevalence will continue to increase as our population ages and the incidence of diseases such as diabetes increases. In many people suffering these problem ....Until something goes wrong, we take it for granted that we can empty our bowels on a regular basis, at a time and place of our choosing. Failure to achieve this is very distressing and substantially diminishes quality of life, if it occurs regularly. Disordered defecation, fecal incontinence and constipation are surprisingly common and their prevalence will continue to increase as our population ages and the incidence of diseases such as diabetes increases. In many people suffering these problems, there is a detectable dysfunction of the sensory nerves in the anal region. These nerves supply information from the anal region to the spinal cord that can cause us to sense activity in our lower bowel and initiate defecation reflexes. These sensory pathways are important for clinical gastroenterology, but remarkably little is known about them. We are now able to investigate what it is the sensory nerves in the anal region sense, what they look like and where they go to in the spinal cord - in a single project. To do this we will use simple, but novel techniques that have been developed in this laboratory in an animal model. Once we know this, we will compare the function of sensory nerves in the anal region in diabetic animals with normal animals. This will give us insight into the role of sensory nerves in the development of fecal incontinence an unpleasant symptom for many people suffering advanced diabetes. My systematic approach will provide understanding of the basic cellular mechanisms and nerve pathways that underlie sensation in the anal region, helping both clinicians and patients understand the cause of defecatory disorders and potentially pointing the way to new therapies and strategies for diagnosis.Read moreRead less
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.
Reconsideration Of The Mechanisms Underlying Movement Changes With Pain
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
Pain changes the way we move. Although undisputed, there is a surprising lack of agreement regarding the underlying mechanisms. This project involves an innovative mix of neurophysiological methods to investigate how the drive to muscle cells from the nervous system is altered during pain. We aim to resolve the perplexing problem of how pain changes our ability to activate muscle. Our findings are likely to provide a clear understanding of the underlying mechanisms and guide rehabilitation.
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.
Mechanism And Treatment Of Sympathetically Maintained Pain
Funder
National Health and Medical Research Council
Funding Amount
$482,962.00
Summary
This project investigates a crucial but neglected element in the mechanism of chronic pain that develops after nerve and tissue injury. In particular, our aim is to establish whether expression of a chemical target of the neurotransmitter noradrenaline increases in the painful skin of affected patients, and whether medication that blocks this target alleviates inflammation and pain. If so, this may open up new avenues for treatment for previously intractable pain syndromes.
Involvement Of Adrenergic Receptors In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$345,473.00
Summary
After nerve or tissue injury including burns, some people will suffer from a condition called neuropathic pain. This is a condition where chronic pain is endured, often totally unrelated to the initial injury or induced by events that would normally not be painful. Our project will determine whether this abnormal pain response is due to an abnormal communication between the nerves that carry pain signals (sensory nerves) and nerves that form part of the sympathetic nervous system, which is part ....After nerve or tissue injury including burns, some people will suffer from a condition called neuropathic pain. This is a condition where chronic pain is endured, often totally unrelated to the initial injury or induced by events that would normally not be painful. Our project will determine whether this abnormal pain response is due to an abnormal communication between the nerves that carry pain signals (sensory nerves) and nerves that form part of the sympathetic nervous system, which is part of autonomic (or involuntary) nervous system. We believe that this abnormal communication is due to an increase in the expression of special receptors called adrenergic receptors, on the sensory nerves. Our project will look at these receptors in the skin of animals that have had pain conditions induced, and also in skin samples from patients who suffer from neuropathic pain that can be classified as sensitive to sympathetic stimulation. By better understanding how neuropathic pain is derived, we can open the door to novel treatment approaches in these difficult to treat conditions.Read moreRead less
What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated with disease, for example, arthritis. Our laboratory has shown that a particular protein is a key mediator of inflammatory pain. The project is to understand how this particular protein promotes pain, including how it sensitzes neurons.
I am a neuroscientist who is fascinated by the ways in which peripheral and spinal neurons respond to environmental changes. By understanding these responses, I hope to develop new ways to treat neural conditions caused by injury, endocrine disturbances and inflammation.
Bile Acid And Neurosteroid Signaling To The Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$587,950.00
Summary
Defects in the secretion of bile into the intestine cause digestive diseases, and abnormal circulating levels of bile acids induce profound itch and abnormal pain sensation. This project examines whether a cell-surface receptor (TGR5) produced by intestinal and sensory neurons mediates actions of bile acids on intestinal functions, itch and pain. The project will define mechanisms of digestive and sensory disorders and identify new therapies for constipation, diarrhoea, itch and pain.