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.
Irritable Bowel Syndrome (IBS) is one of the leading causes of chronic pain both world-wide and in Australia for which there is a lack of treatments. Chronic pain arises from nerve fibres in the colon wall, which fail to 'reset' back to normal following inflammation. Targeting these nerve endings with drugs is a key advance in IBS treatment. This project will identify selective oxytocin analogues that act in the colon to lower pain in sensory nerves thus providing efficacious pain relief in IBS.
Excitatory Interneurons: A Sensory Amplifier For Pathological Pain
Funder
National Health and Medical Research Council
Funding Amount
$649,848.00
Summary
Changes to the nervous system during pathological pain remain poorly understood. This poses a barrier to new and more effective pain therapies. We have recently shown that a population of excitatory nerve cells, which express a protein called calretinin, form an amplifier network within the spinal cord that enhances pain signalling. This application will determine how calretinin-positive nerve cells contribute to pathological pain and can subsequently be targeted to provide pain relief.
Neuropathic pain is particularly difficult to treat and existing medications have considerable side effects. This project will develop a new set of glycine transport inhibitors that have the potential to provide pain relief without side effects.
Developing Subtype-selective Blockers Of Acid-sensing Ion Channels For Treating Peripheral Pain
Funder
National Health and Medical Research Council
Funding Amount
$641,407.00
Summary
Chronic pain is a huge medical problem that affects 1 in 5 adults. There are few drugs available for treating chronic pain, and many of these have limited efficacy and dose-limiting side-effects. Acid-sensing ion channels are proteins that play an essential role in the specialised nerves that sense pain signals. The ultimate goal of this project is to engineer highly selective blockers of these channels that can be used to develop effective analgesics for treating patients with chronic pain.
Chronic pain is a debilitating syndrome caused by damage to tissue and the nervous system, arising from trauma and disease. It is poorly served by current drugs. To identify novel more effective therapies we propose to examine the mechanisms underlying this syndrome. We have identified a novel protein which is involved in synaptic plasticity. We will examine its role the development of chronic pain at the cellular level and how it might be exploited for the treatment of chronic pain.
Decoding Dysfunctional Spinal Cord Circuitry In Chronic Pain.
Funder
National Health and Medical Research Council
Funding Amount
$516,101.00
Summary
Chronic pain is common, with one in five Australians having long-term pain that is serious enough to cause disability. Unfortunately this type of pain is difficult to treat, and current medicines are ineffective in many people, with unwanted side-effects. The aim of this project is to understand how signalling in the spinal cord changes following the development of chronic pain so we can find better strategies to reverse the symptoms and treat pain more effectively.
Identifying The Neural Signature Of Persistent Pain
Funder
National Health and Medical Research Council
Funding Amount
$547,094.00
Summary
Chronic pain affects over 20% of Australians. Despite its high prevalence, it is relativly resistant to current treatment regimes and part of the reason behind our inadequate ability to provide satisfactory pain relief is due to our limited understanding of the pathophysiology that underlies this condition. This proposal will develop a novel understanding of the central neuroplastic changes associated with chronic pain and the role that these changes play in the maintenance of these conditions.
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.
Endometriosis affects up to 10% of reproductive aged women causing a range of debilitating symptoms including pelvic pain and infertility. Our team has discovered that small nerve fibres can be found in the endometrium of women with endometriosis that are not present in women without the condition. We will investigate how these nerve fibres grow and the mechanisms of pain generation. This will potentially allow the development of more targeted and effective treatment modalities.