Piezo2 And Pain - Is There A Role For Piezo2 In Mechanically Induced Bone Pain?
Funder
National Health and Medical Research Council
Funding Amount
$543,848.00
Summary
Pain associated with bone marrow edema, osteoarthritis, bone cancer and fracture puts a significant burden on individuals, society, and the health care system in Australia. A dominant feature of these includes mechanical disturbances of the bone, and this is a trigger for the pain. In this study, we will determine if a newly discovered mechanically gated ion channel (Piezo2) is a key contributor to mechanically induced bone pain and could be a target for development of drugs to treat it.
Discovery And Development Of Better Pain Treatments
Funder
National Health and Medical Research Council
Funding Amount
$9,613,850.00
Summary
Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clini ....Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clinical potential.Read moreRead less
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.
Although chronic pain is a serious clinical problem, treatments for its alleviation have largely failed, in part because they have not been tailored to the specific origin of the pain. This proposal focuses on rheumatoid arthritis, a common and incurrable source of chronic pain. This study will investigate how specific changes in spinal cord nerve cells contribute to chronic arthritic pain. The outcomes will help identify new targets to treat chronic pain in rheumatoid arthritis.
Spinal Cord Injury Pain: Understanding Mechanisms To Develop Treatments
Funder
National Health and Medical Research Council
Funding Amount
$597,675.00
Summary
Spinal cord injury has devastating effects on health and quality of life. Many of the major consequences of injury, such as chronic pain and loss of voluntary voiding, are "invisible" – i.e., they are not as visible as limitations of mobility. Our study aims to define the neurobiological changes that cause development of persistent pain after spinal cord injury and use pharmacological tools to attenuate the development of pain.
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.
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.
Development Of Peripheral Sensory Pathways In Humans
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
To receive the appropriate information about the state of our muscles, joints, organs, and skin we need a properly 'connected' sensory system. Recent evidence suggests traumatic events during early development can alter sensory connections within the spinal cord. This can lead to debilitating movement disorders, digestive diseases, and increased pain. In this study we will examine how peripheral sensory fibres connect with the appropriate nerve cells in the human spinal cord during development.
Targeting GDNF Family Ligand (GFL) Signalling To Treat Inflammatory Bone Pain
Funder
National Health and Medical Research Council
Funding Amount
$329,285.00
Summary
Pain associated with bone marrow oedema syndromes, osteomyelitis, osteoarthritis, fractures and bone cancer causes a major burden on individuals and health care systems in Australia and worldwide. In this application, we will explore specific signalling pathways that we have identified in nerves that code bone pain. This will provide an opportunity for the rational design of highly specific drugs capable of interacting exclusively with molecules that drive pain in these conditions.
THE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES TO DEEP AND SUPERFICIAL PAIN IN HUMAN SUBJECTS
Funder
National Health and Medical Research Council
Funding Amount
$375,750.00
Summary
Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes ....Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes changes in blood pressure, heart rate and motor activity (often in an attempt to remove the source of the pain). The proposed research aims to characterise the cardiovascular and motor patterns associated with pain originating in skin and in muscle and to examine the brain regions that produce these changes. More specifically, microelectrodes will be used to investigate changes in peripheral nerve activity during transient painful skin and muscle events in awake human subjects. In a separate investigation functional magnetic resonance imaging will be used to determine brain sites that are activated by skin or muscle pain.Read moreRead less