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
Importance Of CGRP Alpha In Pain Processing From The Large Intestine
Funder
National Health and Medical Research Council
Funding Amount
$548,289.00
Summary
This project will determine the mechanisms by which sensory nerve endings detect painful stimuli in the large intestine. The project will use a novel genetically modified mouse (that is only available in our laboratory) which allows us, for the first time, to visualize and record directly from the sensory nerve endings that detect painful stimuli and work out how this process occurs. We also identify a specific gene that is essential for detecting painful stimuli from this organ.
Pain Systems Analysis Highlights PI3K Gamma As A Candidate Regulator Of Nociception.
Funder
National Health and Medical Research Council
Funding Amount
$461,810.00
Summary
Chronic pain will affect most of us at one point in our life, and there is a need for new drugs to manage this condition. The goal of this project is to use our computer modeling of genetic data from multiple species to predict new drug targets, and then use mouse models to look at the mechanism of action for predicted drug targets, and validate one potential drug target in particular for its therapeutic abilities to stop chronic pain.
Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of ....Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of VR1 receptor activation and provide information on how the VR1 receptor is regulated. We will determine and compare neurotoxicity of these compounds to capsaicin which is known to possess neurotoxic activity. The outcome of this project may result in effective agents for better pain management.
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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.
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.