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.
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.
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 a combined state-of-the-art genetics approaches in fruit flies, mice, rats, and humans, to identify and validate new genes that contribute to chronic pain, with the clear long term possibility to develop new strategic therapies to treat chronic pain disease.
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.
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
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.
SENSORIMOTOR AND AUTONOMIC DYSREGULATION IN HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES
Funder
National Health and Medical Research Council
Funding Amount
$50,406.00
Summary
Specific genetic mutations can lead to widespread changes in the body. Here we are looking at the congenital Hereditary and Sensory Autonomic Neuropathies, the most common of which primarily affects Eastern European Jews. Affected individuals have difficulty walking and controlling their blood pressure, and also have an indifference to pain. This series of experiments aims to increase our understanding of the underlying neurophysiological disturbances.
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.