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
What Triggers Complex Regional Pain Syndrome After Minor Injury?
Funder
National Health and Medical Research Council
Funding Amount
$958,898.00
Summary
Most people recover from minor trauma but some develop very disabling, difficult to treat, costly pain syndromes. We can identify those at high risk of developing such a syndrome after wrist fracture. By comparing inflammation, immune system function, stress, brain function and behaviour between high and low risk patients, we will take a major step towards understanding, preventing and treating these syndromes.
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
Endocannabinoid-TRP Interactions In Midbrain Analgesic Pathways
Funder
National Health and Medical Research Council
Funding Amount
$586,903.00
Summary
Current pharmacotherapies for chronic pain are often ineffective. The active ingredient of the plant Cannabis sativa, THC, and a number of synthetic cannabinoids have efficacy in these pain states, however, they also produce a spectrum of adverse side-effects. This project will use cellular and behavioural techniques to examine how this cannabinoid system modulates intrinsic pain systems within the midbrain in order provide leads for novel analgesic pharmacotherapies with enhanced efficacy.
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.
Peripheral Neuropathy And Pain: Role Of The Sphingosine Kinase-sphingosine 1-phosphate System
Funder
National Health and Medical Research Council
Funding Amount
$282,905.00
Summary
Understanding the neural mechanisms that generate pathological pain remains one of the essential goals for the development of effective treatments for pain, chronic pain with less side effects. Lipids are able to modulate pain perception. We will determine the role of a molecule named sphingosine 1-phosphate as a basis for the development of therapies for the treatment of neuropathic pain.
Chronic pain is a common and debilitating condition. One in five people in the Australian community have been found to experience chronic pain at any one time. Although there is no evidence of a consistent increase in rates of chronic pain, the rate of permanent disability has increased dramatically in recent decades. This has contributed to the growing cost of chronic pain. For example, back pain is the most common reason for filing workers' compensation claims and leads to loss of 101.8 millio ....Chronic pain is a common and debilitating condition. One in five people in the Australian community have been found to experience chronic pain at any one time. Although there is no evidence of a consistent increase in rates of chronic pain, the rate of permanent disability has increased dramatically in recent decades. This has contributed to the growing cost of chronic pain. For example, back pain is the most common reason for filing workers' compensation claims and leads to loss of 101.8 million workdays annually. The annual costs of medical care for back pain alone have been estimated at $AUD50 billion in the US and $10 billion in Australia. Not only is chronic pain a considerable economic burden, it is also a considerable personal burden to patients. Pain is one of the strongest predictors of poor quality of life and has consistently been found to be associated with high rates of depression. Although there is a large body of research that investigates what factors are associated with chronic pain, there is surprisingly little research that investigates the mechanisms that cause chronicity. Theories of chronic pain suggest that psychological characteristics increase the propensity for people to develop chronic pain. Specifically, theories argue that those people who tend to be fearful of pain will over-attend to painful sensations and avoid pain-provoking activities and as a result are at risk of developing chronic pain. This study will test those theories. If it is found that over-attending to pain does predispose patients to develop chronic pain, this will have important implications for preventing the development of chronic pain. These findings could help to devise early interventions to prevent chronicity and thereby reduce the economic burden to health services and the emotional burden to patients in terms of reduced quality of life.Read moreRead less
Nurses' Pain Management Decisions In The Post Surgery Context: A Naturalistic Study
Funder
National Health and Medical Research Council
Funding Amount
$56,368.00
Summary
In the hospital environment, doctors often prescribe medications for pain using an as required format on the drug order chart. Very often, this form of prescription occurs in the surgical wards of a hospital, where a patient may need a lot of pain relieving medication in the early period following the operation, and very little medication a few days following the operation. In the as required form of prescribing, the nurse caring for the patient has enormous flexibility in determining when and h ....In the hospital environment, doctors often prescribe medications for pain using an as required format on the drug order chart. Very often, this form of prescription occurs in the surgical wards of a hospital, where a patient may need a lot of pain relieving medication in the early period following the operation, and very little medication a few days following the operation. In the as required form of prescribing, the nurse caring for the patient has enormous flexibility in determining when and how much medication should be administered. Previous work has consistently shown that nurses do not administer adequate medication, which often results in poor pain control. Several nurse-related reasons have been proposed for poor pain management, including the fear of addiction, the fear of producing difficulties in breathing, and inadequate education about the medications administered. The focus of previous work has relied on examining small areas in isolation. Primarily, researchers have examined information on the drug order charts following patient discharge from hospital. They have also relied on analysing nurses' views on pain management relating to hypothetical patient situations. Overall, the research fails to address the multiple and interconnected factors faced by the nurse which could impact on pain management. Sources of these factors may be the patient, nurse, medication or environment. Examples of these factors include the presence or absence of the doctor, nurses' communication with doctors and other nurses about patient care, layout of the hospital ward, ward management structure, and methods used by the nurse to assess patient pain. By identifying the complex factors that impinge on decisions for managing pain, this study will provide opportunities to address the barriers that prevent adequate pain management. Nurses will then be in a position to change their practice in order to improve the management of patients' pain.Read moreRead less