Although chronic pain is a serious clinical problem, treatments for its alleviation have largely failed, in part because they have not been tailored to the specific origin of the pain. This proposal focuses on rheumatoid arthritis, a common and incurrable source of chronic pain. This study will investigate how specific changes in spinal cord nerve cells contribute to chronic arthritic pain. The outcomes will help identify new targets to treat chronic pain in rheumatoid arthritis.
Chronic neck pain is difficult to treat and can result in a complex set of symptoms, including dizziness, disturbed vision, and exaggerated pain responses in the upper torso and arms. Thus, there is a need to develop new treatments for this debilitating condition. This project will study how damage to structures in the neck alters the excitability of nerve cells in the upper cervical spinal cord. The results will provide a foundation for development of therapies to treat chronic neck pain.
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.
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
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.
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.
Targeting The Brain To Treat Chronic Pain Of Whiplash Associated Disorder
Funder
National Health and Medical Research Council
Funding Amount
$322,952.00
Summary
Chronic neck pain is the equal leading cause of disability worldwide. Guided by largely disproven structural pathology paradigms, treatment resources are directed to ‘fix’ musculoskeletal abnormalities, with at best small effects. Brain-imaging studies suggest that brain (rather than neck tissue) changes, may instead maintain pain. My research will test new brain-based treatments: The Tactile Training Device, and MoOVi Illusory Exercise Program and their effects on pain, disability and brain.
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.