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
I am a molecular physiologist investigating the structure and function of the inhibitory neurotransmitter glycine receptor (GlyR) and GABA type- A receptor (GABAAR) chloride channels. We are interested in understanding how these receptors open and close
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.
I am a physiologist-pharmacologist examining fundamental mechanisms of chronic inflammatory disease. By defining these mechanisms, I seek to discover the underlying cause of disease and to identify novel strategies for diagnosis and therapy of chronic diseases that are worldwide causes of morbidity and mortality.
I am a neuroscientist- neuropharmacologist determining molecular, cellular, synaptic and behavioural mechanisms of opioid addiction and persistent pain states.
Chronic pain is a debilitating syndrome caused by damage to tissue and the nervous system, arising from trauma and disease. It is poorly served by current drugs. To identify novel more effective therapies we propose to examine the mechanisms underlying this syndrome. We have identified a novel protein which is involved in synaptic plasticity. We will examine its role the development of chronic pain at the cellular level and how it might be exploited for the treatment of chronic pain.
Discovery And Development Of Better Pain Treatments
Funder
National Health and Medical Research Council
Funding Amount
$9,613,850.00
Summary
Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clini ....Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clinical potential.Read moreRead less
Pain has a detrimental impact on ones quality of life and a significant financial impact on the community. Although some of the pathways that code pain in the brain have been defined, it was recently proposed that there also exists a pain-specific pathway in humans. Using human brain imaging, we aim to determine if such a pathway exists and if it is altered in subjects with chronic pain. The existence of such a pathway would significantly aid in the development of better treatment regimes.
Pain Systems Analysis Highlights PI3K Gamma As A Candidate Regulator Of Nociception.
Funder
National Health and Medical Research Council
Funding Amount
$461,810.00
Summary
Chronic pain will affect most of us at one point in our life, and there is a need for new drugs to manage this condition. The goal of this project is to use our computer modeling of genetic data from multiple species to predict new drug targets, and then use mouse models to look at the mechanism of action for predicted drug targets, and validate one potential drug target in particular for its therapeutic abilities to stop chronic pain.
The human genome project was a major advance, allowing for molecular foothold towards an understanding of human diseases. The question now is “what do these genes do, and how do they participate in human disease?” In my lab we are focused on this issue. We use whole genome, functional in vivo screening in the fruit fly to identify novel conserved disease genes, then we use human genetics data to focus on medically relevant candidates, finally we use knockout mice to functionally validate these n ....The human genome project was a major advance, allowing for molecular foothold towards an understanding of human diseases. The question now is “what do these genes do, and how do they participate in human disease?” In my lab we are focused on this issue. We use whole genome, functional in vivo screening in the fruit fly to identify novel conserved disease genes, then we use human genetics data to focus on medically relevant candidates, finally we use knockout mice to functionally validate these new genesRead moreRead less