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
Mechanisms Of Serotonergic And Triptan Mediated Analgesia Within The Midbrain
Funder
National Health and Medical Research Council
Funding Amount
$546,937.00
Summary
Chronic pain requires multiple pharmacological interventions and these are often ineffective. These drugs include those which act on a diverse group of cell-surface proteins, called serotonin receptors. This project will use cellular and whole animal techniques to examine how these agents act within intrinsic pain and anxiety control systems within the brain in order to identify novel analgesic pharmacotherapies with enhanced efficacy and reduced side effects.
Systematic Expansion Of The Clinical Evidence Base In Opioid Prescribing For Refractory Dyspnoea At The End Of Life
Funder
National Health and Medical Research Council
Funding Amount
$414,535.00
Summary
Morphine can relieve breathlessness in the palliative setting. But many important questions remain. What is the best dose, should the dose change over time, do different medications provide the same relief, and how common is dyspnoea in the general population? This three part project will extend our knowledge to answer these questions. Population data will provide critical background to plan best care for future palliative patients distressed by breathlessness.
Evaluating Novel Methods For Delivering Non-pharmacological Interventions For Dyspnoea In Cancer Patients
Funder
National Health and Medical Research Council
Funding Amount
$506,036.00
Summary
Dyspnoea, or breathlessness, can be a common and distressing problem for people with lung cancer. This study aims to test the effectiveness of a patient education program which includes breathing exercises and psychosocial support for helping patients with lung cancer to control their dyspnoea. The education program is novel in that it applies best available evidence about methods for providing information and support for people with cancer to enhance the effectiveness of the intervention. The s ....Dyspnoea, or breathlessness, can be a common and distressing problem for people with lung cancer. This study aims to test the effectiveness of a patient education program which includes breathing exercises and psychosocial support for helping patients with lung cancer to control their dyspnoea. The education program is novel in that it applies best available evidence about methods for providing information and support for people with cancer to enhance the effectiveness of the intervention. The study will test whether the intervention reduces a patients' feelings of breathlessness, improves their ability to function, and minimises their emotional distress. The intervention being evaluated in this study has been developed so that it can be readily incorporated into routine clinical practice. The study will also examine the effectiveness of this intervention over time, to identify which patients may benefit from this approach and at what times the intervention may be of most use. The information gained from this study will provide more specific guidance to practitioners for targeting intervention approaches to each individual patient's needs.Read moreRead less
Disorders of pain sensation due to nerve damage are common, debilitating and difficult to treat. Nerve damage often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. Pain is one of the commonest clinical problems, and yet it is often accepted or taken for granted. The outcome of this work will be an increased understanding of the way in which nerve injury leads to spontaneous pain and increased sensitiv ....Disorders of pain sensation due to nerve damage are common, debilitating and difficult to treat. Nerve damage often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. Pain is one of the commonest clinical problems, and yet it is often accepted or taken for granted. The outcome of this work will be an increased understanding of the way in which nerve injury leads to spontaneous pain and increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.Read moreRead less
Mechanisms Of Endogenous Cannabinoid Mediated Analgesia Within The Midbrain
Funder
National Health and Medical Research Council
Funding Amount
$518,820.00
Summary
While opioid analgesics such as morphine are the most important drugs used to treat moderate to severe pain, their usefulness is limited by side effects such as tolerance and respiratory depression. In addition, clinically relevant neuropathic chronic pain syndromes (caused by nervous system damage) are relatively resistant to opioids. Animal studies have shown that the active ingredient of the plant Cannabis sativa, THC, and a number of synthetic cannabinoids are analgesic in acute pain models, ....While opioid analgesics such as morphine are the most important drugs used to treat moderate to severe pain, their usefulness is limited by side effects such as tolerance and respiratory depression. In addition, clinically relevant neuropathic chronic pain syndromes (caused by nervous system damage) are relatively resistant to opioids. Animal studies have shown that the active ingredient of the plant Cannabis sativa, THC, and a number of synthetic cannabinoids are analgesic in acute pain models, and interestingly, in chronic neuropathic pain models. Unfortunately, cannabinoid also produce a spectrum of adverse side-effects. Administered cannabinoids such as THC produce their physiological effects by mimicking the actions of the body's own cannabinoids (endocannabinoids) by activating cell-surface proteins, called cannabinoid receptors. The endocannabinoid neurotransmitter system is emerging as a potential therapeutic target. For example, it has recently been shown that analgesia induced by physiological stressors is partly mediated by endocannabinoids within the brain. In addition, novel endocannabinoid breakdown inhibitors have some efficacy in animal models of anxiety and chronic pain. Several brain regions are known to play a pivotal role in the analgesic actions of exogenous and endogenous cannabinoids. In previous studies I have identified the cellular mechanisms by which exogenously applied opioids and cannabinoids produce their analgesic effects in single brain cells. However, the mechanisms of endocannabinoid actions within these brain regions are unknown. The proposed study will determine the cellular actions of endogenously released cannabinoids in normal animals and in chronic pain states. Parallel studies will examine the effect of modulation of the endocannabinoid system in animal models of pain. These techniques have the potential to identify novel endocannabinoid analgesic pharmacotherapies with enhanced efficacy and reduced side effects.Read moreRead less