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Enkephalin Metabolism In Cardiac Ischemia, Heart Failure And Cardiac Surgery
Funder
National Health and Medical Research Council
Funding Amount
$327,037.00
Summary
It has recently been discovered in animal studies that heart muscle can make its own opioid proteins. Previously, it was thought that only nerves made and released opioids. We have recently found that a class of opioids called enkephalins are made and then depleted from the heart during the stress of oxygen and nutrient deprivation. Enkephalins have been found to have potent metabolic effects on the heart. Previous work has shown that opioids can protect the heart against injury incurred during ....It has recently been discovered in animal studies that heart muscle can make its own opioid proteins. Previously, it was thought that only nerves made and released opioids. We have recently found that a class of opioids called enkephalins are made and then depleted from the heart during the stress of oxygen and nutrient deprivation. Enkephalins have been found to have potent metabolic effects on the heart. Previous work has shown that opioids can protect the heart against injury incurred during disease that restricts energy and oxygen supply to the blood vessels and heart. We wish to demonstrate this for the first time in human heart, and we will explore whether the production of enkephalins is altered by the stresses of cardiac surgery and heart failure. Understanding how the human heart attempts to protect itself in disease and how enkephalins work under these conditions, may prove valuable in the development of new drug therapy with synthetic drugs which mimic the action of enkephalins for heart protection during cardiac surgery, heart transplantation and ischemic heart disease. We will test whether specific enkephalins may be used to improve donor heart viability for transplantation by improving the duration and quality of preservation during storage. Understanding what happens to enkephalin production and metabolism in the failing hearts of patients may allow us to find new therapeutic targets in heart failure.Read moreRead less
Pharmacological Strategies To Enhance Endogenous Opioid Actions In Pain Circuits.
Funder
National Health and Medical Research Council
Funding Amount
$1,318,226.00
Summary
Boosting endogenous opioid actions in our brain may allow us to utilize this system to reduce pain and the related disability without the addiction and overdose threat associated with opioid drugs. We have shown that we can enhance endogenous opioid actions using two pharmacological strategies. We will now determine how we can use these strategies to enhance endogenous opioid regulation of the neural function and behaviours important in pain and related anxiety disorders.
Pain is a prevalent condition and a major cause of disease burden. The research program will address important questions in the clinical management of pain to reduce its the enormous burden. The program will: 1) investigate whether opioid medicines and oral steroids are effective in treating acute low back pain and neck pain, and sciatica, and 2) assess and improve the appropriate use of strong pain medicines in primary care.
While we need to consume salt, too much can be harmful and is in fact directly linked to ~5% of deaths annually in Australia. We have identified a system in the brain that regulates salt intake. Going forwards we will fully elucidate the pathway(s) implicated in regulation of salt intake, thereby identifying strategies to reduce excessive salt consumption.
The Extent And Impact Of Pharmaceutical Opioids For Chronic Non-cancer Pain
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
There have been dramatic increases in the use of pharmaceutical opioids (PO) for chronic non-cancer pain (CNCP), despite limited data on their long-term effectiveness and an increase in associated harm. This Fellowship provides critical new data to inform both clinicians and policymakers on the global extent of PO for CNCP, trajectories of problematic use and associated morbidity and a unique evaluation of the impact of real-time prescription monitoring program to reduce these harms.
Adouble-blind Placebo Contorolled Study Of Subcutaneous Ketamine In The Management Of Cancer Pain
Funder
National Health and Medical Research Council
Funding Amount
$50,000.00
Summary
Palliative care teams are studying an anaesthetic, ketamine, used at low doses for cancer pain which is not responsive to opioid drugs. Clinical experience suggests ketamine may help in neuropathic pain, which is due to nerve damage and is common in cancer. The study involves five days of treatment at three doses of ketamine, to see how well pain is controlled on each dose. The highest dose given will be that which gives good pain control. The study compares ketamine with a placebo, and patients ....Palliative care teams are studying an anaesthetic, ketamine, used at low doses for cancer pain which is not responsive to opioid drugs. Clinical experience suggests ketamine may help in neuropathic pain, which is due to nerve damage and is common in cancer. The study involves five days of treatment at three doses of ketamine, to see how well pain is controlled on each dose. The highest dose given will be that which gives good pain control. The study compares ketamine with a placebo, and patients keep on their usual pain medicines. Participants are randomised to have ketamine or the placebo. The study looks at pain control, quality of life, ketamine side effects, and change in need for usual pain medicines. This is the first national clinical study of a new palliative care research network, the Palliative Care Clinical Trials Collaborative (PaCCSC). It is hoped that if ketamine is proven safe and effective in difficult cancer pain, it will be more easily available for cancer patients.Read moreRead less
Novel Analgesic Approaches: Harnessing Functional Interactions Between Sodium Channels And Opioids
Funder
National Health and Medical Research Council
Funding Amount
$329,076.00
Summary
Chronic pain is a debilitating condition that affects the life of one five Australians and has significant socioeconomic impact. Currently available pain killers often do not work, or have intolerable side effects. We have discovered that combination treatment with opioids and a novel venom-derived compound discovered by us provides effective pain relief. The aim of this project is to understand the mechanisms underlying this synergistic effect to develop new treatment approaches for pain.
Most deaths from non-illicit drugs are caused by prescribed opioids and are nearly always due to respiratory arrest during sleep. However, no study has assessed the effect of opioids on vital respiratory drives during sleep. In addition, sleep apnea has been identified as a major risk factor for postoperative morbidity and mortality, while no study investigated how to identify those sleep apnea patients most at risk of opioids. Our proposed studies aim to address these gaps in knowledge.
Combating Escalating Harms Associated With Pharmaceutical Opioid Use
Funder
National Health and Medical Research Council
Funding Amount
$925,767.00
Summary
Increases in opioid use have been accompanied by increased opioid harms. But there is a lack of population-level evidence about drivers of long-term prescribed opioid use, dependence, overdose and other harms. Using linked data, we will fill these gaps using a cohort of all people in NSW prescribed opioids since 2002, linked to datasets containing information on health, social and health service utilisation, that will permit a comprehensive assessment of the risks of all prescribed opioids.