A Pharmacological Approach To Define The Contribution Of Nav1.7 To Pain Pathways
Funder
National Health and Medical Research Council
Funding Amount
$501,467.00
Summary
Chronic pain is a debilitating condition that affects the life of one in five Australians and has significant socioeconomic impact. Currently available pain killers often do not work, or have intolerable side effects. We have discovered the most selective blocker for a specific type of sodium channel that is a known pain target and will use this novel molecule to gain insight into the mechanisms of pain and to develop new pain killers.
Stimulus Induced Synaptic Plasticity In The Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$428,777.00
Summary
Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating ....Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating doses required for adequate pain relief and the limited efficacy of current drug therapies in some clinically important pains states. The persistence of pain after the original injury has resolved suggest the development of adaptations that result in the ongoing pain. The changes in neurobiology underlying persistent pain are poorly defined. A better understanding of this neurobiology will result in better therapeutic approaches to persistent pain. The amygdala is a brain region that is important for pain processing, endogenous analgesia and emotion. A neuronal pathway that delivers information about pain to the amygdala has recently been shown to be critical for the development of persistent pain. Little is known about whether this critical neuronal pathway is modified by pain. This project will determine using electrical and chemical techniques how a brief or persistent painful stimulus changes the delivery of painful information to the neurons in the amygdala. The changes produced by a brief painful stimulus likely represent the initial changes in the development of a persistent pain state. This information may allow us to more fully understand the transition from acute to persistent pain and the changes defined may be sensitive to pharmacological modulation. Preventing or inhibiting these pain induced changes may provide better treatment for persistent pain or ideally prevent people undergoing the transition from acute to persistent pain.Read moreRead less
Targeted Ablation Of Sensory Neurons And Glial Cells With A View To Relieving Neuropathic Pain.
Funder
National Health and Medical Research Council
Funding Amount
$280,910.00
Summary
In Australia more than half of chronic pain patients are diagnosed with neuropathic pain resulting from nerve injury. This type of pain persists long after injury has healed and is associated with spontaneous bursts of excruciating pain and altered sensory processing symptoms which can make even the light touch of clothing intolerable. Neuropathic pain is highly resistant to even the most intense and drastic pain treatments. Much research has been devoted to understanding neuropathic pain in ter ....In Australia more than half of chronic pain patients are diagnosed with neuropathic pain resulting from nerve injury. This type of pain persists long after injury has healed and is associated with spontaneous bursts of excruciating pain and altered sensory processing symptoms which can make even the light touch of clothing intolerable. Neuropathic pain is highly resistant to even the most intense and drastic pain treatments. Much research has been devoted to understanding neuropathic pain in terms of changes in nerve cell (neuron) structure, function and chemistry. Whilst we have learned a lot about how neurons contribute to neuropathic pain, it has since become clear that cells other than neurons (namely neuronal support cells called glia) also play a significant role in the production and continuation of pain after nerve injury. Thus, it may be that pain therapies which currently focus on stopping or minimising the changes in neurons after nerve injury are only doing half the job when it comes to relieving such pain. Targeted therapies aim to affect or kill particular groups of cells with the hope of further understanding their role in the disease progression or eliminating their contribution to the disease state to produce relief. This can be done using a toxin linked to a vehicle that only binds to a particular cell type and which, upon uptake, causes the cell to suicide. Targeting neurons and glia responsible for neuropathic pain may hold a key to relieving this pain state. This project aims to further understand the contributions of neurons and glia to the production of neuropathic pain and aims to determine the effectiveness of synergistic targeted therapies that kill both the neurons and glia responsible for neuropathic pain production. It is hoped that killing these cells will effectively remove their input to the production and continuation of neuropathic pain and may offer a new avenue for neuropathic pain treatment in the future.Read moreRead less
Central pathways regulating visceral pain. This project aims to investigate the neural pathways within the spinal cord and brain processing colorectal pain perception. The project aims to identify the spinal cord neurons relaying colorectal signalling into the brain and the influence of descending modulation from the brainstem upon these pathways. The outcomes will greatly benefit fundamental understanding of the central pathways processing visceral pain.
Transcriptional control of neural stem cell differentiation during development and disease. Understanding the molecular mechanisms that control how neural stem cells differentiate is critical to provide potential therapeutic treatment for neurodegenerative diseases and for brain cancer. This project will aim to discover, using an animal model system, the genes and molecules regulating these key biological processes.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100074
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genet ....Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genetic and acquired disorders across the life-span. Remote viewing and analysis capabilities will help overcome the 'tyranny of distance', increasing national access to the facility. Repositories of digitised images will increase the availability of valuable research material to other Australian and international researchers.Read moreRead less
Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occul ....Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occult segmental pattern in adult mice. This work will give us a new way of understanding the organisation of brainstem centres that control breathing, cardiovascular functions and emotional states.Read moreRead less
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less
Cellular and Neurochemical Basis of Drug Addiction. Addiction to the major drugs of abuse, including heroin, amphetamines, cocaine, nicotine and alcohol damage the lives and cause premature death of more than 20% of Australians. Addiction produces long-term disruption of brain processes that lead to loss of control over urges to consume drugs and persistent cycles of relapse to drug taking. This research will apply new neurochemical approaches to discover mechanisms of disrupted brain function t ....Cellular and Neurochemical Basis of Drug Addiction. Addiction to the major drugs of abuse, including heroin, amphetamines, cocaine, nicotine and alcohol damage the lives and cause premature death of more than 20% of Australians. Addiction produces long-term disruption of brain processes that lead to loss of control over urges to consume drugs and persistent cycles of relapse to drug taking. This research will apply new neurochemical approaches to discover mechanisms of disrupted brain function that occur during development of addiction and relapse that are critical for development of better strategies to treat the disorder. Read moreRead less