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.
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.
Decoding Dysfunctional Spinal Cord Circuitry In Chronic Pain.
Funder
National Health and Medical Research Council
Funding Amount
$516,101.00
Summary
Chronic pain is common, with one in five Australians having long-term pain that is serious enough to cause disability. Unfortunately this type of pain is difficult to treat, and current medicines are ineffective in many people, with unwanted side-effects. The aim of this project is to understand how signalling in the spinal cord changes following the development of chronic pain so we can find better strategies to reverse the symptoms and treat pain more effectively.
Identifying The Neural Signature Of Persistent Pain
Funder
National Health and Medical Research Council
Funding Amount
$547,094.00
Summary
Chronic pain affects over 20% of Australians. Despite its high prevalence, it is relativly resistant to current treatment regimes and part of the reason behind our inadequate ability to provide satisfactory pain relief is due to our limited understanding of the pathophysiology that underlies this condition. This proposal will develop a novel understanding of the central neuroplastic changes associated with chronic pain and the role that these changes play in the maintenance of these conditions.
Stimulus Induced Synaptic Plasticity In The Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$428,777.00
Summary
Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating ....Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating doses required for adequate pain relief and the limited efficacy of current drug therapies in some clinically important pains states. The persistence of pain after the original injury has resolved suggest the development of adaptations that result in the ongoing pain. The changes in neurobiology underlying persistent pain are poorly defined. A better understanding of this neurobiology will result in better therapeutic approaches to persistent pain. The amygdala is a brain region that is important for pain processing, endogenous analgesia and emotion. A neuronal pathway that delivers information about pain to the amygdala has recently been shown to be critical for the development of persistent pain. Little is known about whether this critical neuronal pathway is modified by pain. This project will determine using electrical and chemical techniques how a brief or persistent painful stimulus changes the delivery of painful information to the neurons in the amygdala. The changes produced by a brief painful stimulus likely represent the initial changes in the development of a persistent pain state. This information may allow us to more fully understand the transition from acute to persistent pain and the changes defined may be sensitive to pharmacological modulation. Preventing or inhibiting these pain induced changes may provide better treatment for persistent pain or ideally prevent people undergoing the transition from acute to persistent pain.Read moreRead less
The Role Of Presynaptic Inhibition In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$466,045.00
Summary
Inhibitory nerve cells in the spinal cord are thought to play an important role in governing the interaction between painful and non-painful stimuli. Defects in this process underlie allodynia, an important symptom of neuropathic pain. We will use recent advances in genetic techniques (optogenetics) to manipulate and study how inhibitory nerve cells separate touch and pain signalling in the spinal cord of normal and neuropathic animals.
Fibromyalgia: Investigating The Prefrontal Cortex And Its Role In Novel Treatment Approaches
Funder
National Health and Medical Research Council
Funding Amount
$338,110.00
Summary
Fibromyalgia, a chronic pain condition, is experienced by 1-3% of Australians. Despite this high number, the cause of fibromyalgia is still unknown with no effective treatment options. In the proposed investigations I will use state of the art neuroscientific paradigms to explore the brain basis of fibromyalgia and utilise novel brain stimulation protocols to provide long-lasting pain relief.
The fundamental problem with pain is that it cannot be seen. We can see injury, but pain and injury are quite often not related. Brain imaging has demonstrated consistent patterns of activity when we feel pain, and long-term changes that happen in chronic, i.e. persistent, painful disorders. This project will use the best technology available to investigate the basics of how our brains perceive pain, and to shed light on some of the brain mechanisms that underpin chronic pain.
Pain has a detrimental impact on ones quality of life and a significant financial impact on the community. It has recently been revealed that chronic pain is associated with altered brain anatomy and function. Using human brain imaging, we aim to determine the underlying reason for these changes by following individuals during the development of pain. Defining the mechanism underlying pain will aid in the development of better treatment regimens.
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.