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.
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.
Ion Channels Underlying Inflammatory And Post-inflammatory Visceral Mechanical Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$453,439.00
Summary
Inflammation causes tissue damage that triggers ion channels within sensory nerve fibres to produce greater signals in response to mechanical events, causing acute pain. In chronic pain, although the inflamed tissue has healed, sensory nerve fibres fail to "reset" back to normal. Often chronic pain is more severe than acute pain. This project will identify which ion channels are responsible for signalling acute and chronic visceral pain, explaining why sensory nerve fibres fail to reset.
This is a study of the senses which arise from our muscles and which tell us where our different body parts are, at any point in time. These senses, collectively called proprioception, are also involved in the automatic, unconscious control of our muscles. So, ultimately, they allow us to stand and to move freely with precision and confidence, even in the dark. One of these senses, the sense of effort or of heaviness, is believed to be generated within the brain. It intensifies when we become fa ....This is a study of the senses which arise from our muscles and which tell us where our different body parts are, at any point in time. These senses, collectively called proprioception, are also involved in the automatic, unconscious control of our muscles. So, ultimately, they allow us to stand and to move freely with precision and confidence, even in the dark. One of these senses, the sense of effort or of heaviness, is believed to be generated within the brain. It intensifies when we become fatigued. These experiments will be concerned with finding out more about how this works. We have a method that uses magnetic stimulation of the brain to change its control of our muscles. Using it we will learn how this sense is generated. When we close our eyes and move our limbs we realise that we know exactly where they are at any point in time. It remains uncertain exactly how this information is generated within the nervous system. One idea, arising from some recent experiments which we want to test, is that as we move the limb, the skin over the moving parts is stretched and stretch-sensitive nerve endings in the skin provide us with information about the movement. Alternatively, perhaps it is the effort we exert to maintain limb position against the force of gravity which tells us where the limb is. In another recent study we have found that when a muscle has become painful from excessive exercise or from some local strain injury, our ability to control the muscle and so move the limb is no longer as effective. We want to study the underlying nervous mechanisms responsible for the changes in movement control. Are they designed to spare the muscle while it recovers from injury? How are they brought about? All of this work is important for a better understanding of ourselves, for a better clinical diagnosis when something goes wrong and for improved treatment of diseased or injured muscles.Read moreRead less
Mechanisms Of Body Representation And The Sensory Consequences Of Stroke
Funder
National Health and Medical Research Council
Funding Amount
$408,842.00
Summary
How does the brain control movement without vision? We cannot see our mouth but can easily put food in it. The brain uses a combination of sensory signals and stored models of the body, to control movement. The body models, and their interaction with sensory information, is not well understood. but they are disrupted by common clinical disorders. This research project investigates unsolved questions about the body model including how it is affected by stroke.
Efferent Control Circuitry Of The Auditory Brainstem
Funder
National Health and Medical Research Council
Funding Amount
$406,306.00
Summary
Detection of important sounds within a noisy background is a crucial function of the mammalian hearing system and defects in this function impair social interaction, learning and development. In addition, activity in the brain needs to be carefully regulated by intrinsic circuitry in order to prevent excessive activity responsible for conditions such as tinnitus. The mechanisms by which the brain achieves this are poorly understood and this project aims to improve our understanding of some of th ....Detection of important sounds within a noisy background is a crucial function of the mammalian hearing system and defects in this function impair social interaction, learning and development. In addition, activity in the brain needs to be carefully regulated by intrinsic circuitry in order to prevent excessive activity responsible for conditions such as tinnitus. The mechanisms by which the brain achieves this are poorly understood and this project aims to improve our understanding of some of the brain circuits involved.Read moreRead less
The human brain has many subdivisions (�areas�) that are dedicated to vision, but in many cases their functions remain unclear. This project will study an area located deep in the brain, about which very little is known, and which appears to be affected from early stages in conditions such as Alzheimer�s disease. By understanding the patterns of electrical activity of cells in this region, and their connections with other brain areas, we hope to decipher their contribution to sensory cognition.
Dendritic Activity And Neuronal Output During Sensory Perception
Funder
National Health and Medical Research Council
Funding Amount
$832,748.00
Summary
A fundamental goal of neuroscience is to understand how sensory experiences arise from activity in the brain. This is no easy feat and is the basis of the research in this proposal. Here, using cutting edge recording techniques, the activity of brain cells within the cortex will be measured during sensory-based behavioural tasks. This research will provide insight into therapeutic approaches to numerous brain diseases where sensory processing is compromised.
Use Of A Novel Technique To Identify The Sensory Nerve Endings That Respond To Painful Stimuli In The Upper Gastrointestinal Tract And Characterize Their Mechanisms Of Activation
Funder
National Health and Medical Research Council
Funding Amount
$353,243.00
Summary
Many people experience pain in their upper gastrointestinal tract. Unlike the skin, however, we have no idea where the sensory nerve endings that detect pain are located in this part of the body, and no clear understanding of how these nerve endings are activated to cause pain. This project will utilise a novel technique recently developed by the CIA to finally identify and record directly from the sensory nerve endings that detect painful stimuli in the upper gastrointestinal tract and characte ....Many people experience pain in their upper gastrointestinal tract. Unlike the skin, however, we have no idea where the sensory nerve endings that detect pain are located in this part of the body, and no clear understanding of how these nerve endings are activated to cause pain. This project will utilise a novel technique recently developed by the CIA to finally identify and record directly from the sensory nerve endings that detect painful stimuli in the upper gastrointestinal tract and characterise the mechanisms underlying their activation.Read moreRead less
Understanding How Inflammatory Bowel Disease Causes Hypersensitivity Of Colonic Sensory Nerve Endings And Increased Abdominal Pain
Funder
National Health and Medical Research Council
Funding Amount
$589,466.00
Summary
Patients with inflammatory bowel disease (IBD) commonly experience increased abdominal pain. This project utilises two novel techniques developed by the Chief investigator, that allow us to understand how inflammation of the large intestine leads to increased pain sensations. This project will use these new techniques to identify, for the first time, the sensory nerve endings that detect painful stimuli from within the large intestine; and how these nerve endings become hyperexcitable during inf ....Patients with inflammatory bowel disease (IBD) commonly experience increased abdominal pain. This project utilises two novel techniques developed by the Chief investigator, that allow us to understand how inflammation of the large intestine leads to increased pain sensations. This project will use these new techniques to identify, for the first time, the sensory nerve endings that detect painful stimuli from within the large intestine; and how these nerve endings become hyperexcitable during inflammation to cause increased abdominal pain.Read moreRead less