Transcriptional Regulation Of Nociceptor Function And Extreme Genetic Pain Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,007,462.00
Summary
Disorders involving untreatable pain have a devastating impact on a patient’s quality of life. To better treat these conditions, we require a basic understanding of how sensory neurons work. In this study we will define the genetic network involved in regulating pain-sensing neurons. We will then search the genome of pain patients looking for coding mutations within this pain transcriptional network, and we will prove these mutations are causative in fly and mouse systems.
Intrinsic Hearing Protection Mechanisms: A Pathway To Prevention Of Noise-induced Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$625,900.00
Summary
Noise-induced hearing loss (NIHL) is a significant contributor to the total burden of disease. We recently determined that when the ear is exposed to sustained noise, the cochlea is protected from damage by activation of a specific (P2X2) receptor, evident as reversible hearing adaptation. This study will determine the downstream signalling from this receptor. This will support assessment of vulnerability to NIHL and contribute to development of hearing therapeutics.
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
Does The Complement System Contribute To Neuropathic Pain?
Funder
National Health and Medical Research Council
Funding Amount
$262,958.00
Summary
Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes ....Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes to neuropathic pain. We have evidence that inflammatory responses play a key role in initiating neuropathic pain. Other evidence suggests that the immune system contributes to neurological diseases and accompanying pain (e.g. Guillain-Barr syndrome and multiple sclerosis). We plan to test the idea that a component of the immune system known as the complement pathway contributes to the development of neuropathic pain following peripheral nerve injury. The outcome of this work will be a better understanding of the way in which nerve injury leads to chronic disorders of pain, including increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.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.