Mechanisms Underlying Increased Cardiac And Renal Noradrenaline Spillover During Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$492,681.00
Summary
Heart failure is associated with increased release of the neurotransmitter noradrenaline from sympathetic nerves to the heart and the kidney. The raised levels of this neurotransmitter in the heart and the kidney are harmful and lead to reduced survival in heart failure patients. This project will increase our understanding of the mechanisms that control noradrenaline release and may lead to better treatment paradigms to target the detrimental increase in release in heart failure.
The brain regulates body temperature by a series of mechanisms, including the control of how much blood flows to the skin to lose or retain heat. The project aims to locate the brain temperature receptors and brain pathways that do this, using an animal model, the rat. At present they are not known.
The Splanchnic Anti-inflammatory Pathway: The Real Inflammatory Reflex
Funder
National Health and Medical Research Council
Funding Amount
$613,466.00
Summary
The brain strongly influences immune function through a neural reflex: the inflammatory reflex. This reflex was recently revised and a new model for its efferent arm, in stark contrast with the existing version, was proposed: the motor pathway of this reflex is purely sympathetic and travels through the splanchnic nerves. The aim of this project is to define the peripheral and central neural pathway of this reflex. Future improvements in health and medical knowledge will follow
Inadequately controlled blood pressure remains the leading cause of death world wide despite the availability of numerous effective drugs. We have successfully pioneered a catheter-based approach using radiofrequency-energy to disrupt renal nerves and lower blood pressure in patients with resistance to conventional drug treatment. We now aim to test the role of this ground-breaking technology as a potential cure (blood pressure control without antihypertensive medication) for hypertension.
Neural Control Of Colorectal Function And Identification Of Sites Of Drug Action
Funder
National Health and Medical Research Council
Funding Amount
$375,489.00
Summary
Constipation is a considerable problem, especially in the elderly; it occurs in 20-25% of people over 65 and in about 50% of people in nursing homes. It is also a significant concern for children, with up to 30% being affected. There are no adequate treatments and the majority of people are dissatisfied with their management. We have discovered a class of compounds that stimulate defecation. In this project we will test the effectiveness of these compounds to relieve constipation.
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.
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.
Hypothalamic Orexin Neurons And The Medullary Sympathoadrenal Centre: A Key Role In Glucose Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$577,957.00
Summary
Hypoglycaemia or low blood sugar is a major side-effect of the treatment of diabetes. Exposure to hypoglycaemia results in changes in the brain (neuroplasticity) that reduce the awareness of hypoglycaemia, often with serious consequences. Hypoglycaemia triggers the production of several hormones including adrenaline which restore normal blood glucose. This process is incompletely understood. This research project will identify key components of the neurocircuitry that controls blood sugar.
Chronic inflammation underlies common and debilitating diseases and causes pain by unknown mechanisms. There is an urgent need to gain a deeper understanding of the mechanisms of chronic pain, which will allow the development of improved therapies with fewer side-effects. Our research program investigates the mechanisms of pain that are associated with inflammatory bowel disease and irritable bowel syndrome, with the goal of developing more effective and selective therapies.
Imaging The Activation Of Sensory Nerve Endings That Detect Pain In The Colorectum
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
Within the gastrointestinal tract are sensory nerve endings that detect painful stimuli. In this project a new technique has been developed that allows us to monitor and record the activation of the particular sensory nerve endings that detect painful stimuli. This project will determine how these sensory nerve endings detect pain and how drugs might be used to relieve these unpleasant sensations arising from the gut wall.