How Spinal Afferent Nerves Cause Vasodilation Of Mesenteric Arteries
Funder
National Health and Medical Research Council
Funding Amount
$353,250.00
Summary
Healthy function of the gastrointestinal tract requires an adequate blood supply during periods of varying demand. Inadequate blood supply to the gut contributes to disorders ranging in severity from mild through to lethal. Reduced blood supply to the gut is a trigger for multiple organ failure syndrome; a leading cause of death in critically ill patients following major surgery, trauma or haemorrhage. It is believed that damage to the lining of the gut, during periods of reduced flow, trigger i ....Healthy function of the gastrointestinal tract requires an adequate blood supply during periods of varying demand. Inadequate blood supply to the gut contributes to disorders ranging in severity from mild through to lethal. Reduced blood supply to the gut is a trigger for multiple organ failure syndrome; a leading cause of death in critically ill patients following major surgery, trauma or haemorrhage. It is believed that damage to the lining of the gut, during periods of reduced flow, trigger inflammatory mechanisms throughout the body. Mesenteric ischaemia is a disorder which occurs as a chronic, non-occlusive form, or as acute episodes, which are often lethal, . Temporary increases in blood supply are also known to play a vital role in protecting the gut from acid, toxins and attack by pathogens. The major mechanism underlying increases in bloody supply is dilation of arterial vessels. This occurs focally, at the site of damage, via local mechanisms, but this is supplemented by a more widespread dilation of arteries upstream, mediated by branches of sensory neurones that innervate blood vessels directly. Currently, there is no information about how these sensory neurones are activated. This is crucial to understand how they work. We hypothesise that these sensory neurones are activated by chemical and mechanical stimuli in the gut wall, which make them release vasodilator chemicals onto the arteries upstream and thus amplify the local increases in blood flow. We will test this by recording from sensory nerves, identifying the ones which project to blood vessels and determine which chemicals and mechanical stimuli they are excited by. We will then fill them with dye, using a method that we have recently developed, to visualise their branching patterns both inside and outside the gut wall. In this way, we will understand how this powerful protective mechanism is activated at times of need, and how it may fail under some circumstances.Read moreRead less
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
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.
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.