Glaucoma is a progressive, poorly understood blinding disease with limited treatment options. It is characterised by the death of the nerve cells in the eye whose fibres form the optic nerve. Results obtained in the current proposal will lead to a better understanding of key features of the early stages of the disease and, additionally, will explore the potential of a novel therapeutic approach based on regeneration of damaged nerve fibres within the optic nerve.
Does The Complement System Contribute To Neuropathic Pain?
Funder
National Health and Medical Research Council
Funding Amount
$262,958.00
Summary
Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes ....Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes to neuropathic pain. We have evidence that inflammatory responses play a key role in initiating neuropathic pain. Other evidence suggests that the immune system contributes to neurological diseases and accompanying pain (e.g. Guillain-Barr syndrome and multiple sclerosis). We plan to test the idea that a component of the immune system known as the complement pathway contributes to the development of neuropathic pain following peripheral nerve injury. The outcome of this work will be a better understanding of the way in which nerve injury leads to chronic disorders of pain, including increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.Read moreRead less
Understanding The Role Of Regulatory T Cells In Chronic Pain Following Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$587,046.00
Summary
Neuropathic pain is a debilitating condition of chronic pain that develops after damage to the nervous system, and lacks an effective treatment. This project focuses on the novel hypothesis that the immunosupressive regulatory T cells and their mediators play a critical role in controlling neuroinflammation and pain hypersensitivity following peripheral nerve injury. This study promises to enhance our understanding of the neuroimmune activation in neuropathic pain and offers novel approaches for ....Neuropathic pain is a debilitating condition of chronic pain that develops after damage to the nervous system, and lacks an effective treatment. This project focuses on the novel hypothesis that the immunosupressive regulatory T cells and their mediators play a critical role in controlling neuroinflammation and pain hypersensitivity following peripheral nerve injury. This study promises to enhance our understanding of the neuroimmune activation in neuropathic pain and offers novel approaches for pain management.Read moreRead less
Deciphering The Mechanisms For Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$496,321.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries The results of these experiments will provide important information on the the initial growth and targeting of these nerve cells which may have implications for regeneration of these as well as other nerve cells.Read moreRead less
THE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES TO DEEP AND SUPERFICIAL PAIN IN HUMAN SUBJECTS
Funder
National Health and Medical Research Council
Funding Amount
$375,750.00
Summary
Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes ....Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes changes in blood pressure, heart rate and motor activity (often in an attempt to remove the source of the pain). The proposed research aims to characterise the cardiovascular and motor patterns associated with pain originating in skin and in muscle and to examine the brain regions that produce these changes. More specifically, microelectrodes will be used to investigate changes in peripheral nerve activity during transient painful skin and muscle events in awake human subjects. In a separate investigation functional magnetic resonance imaging will be used to determine brain sites that are activated by skin or muscle pain.Read moreRead less
Spinal Cord Injury Pain: Understanding Mechanisms To Develop Treatments
Funder
National Health and Medical Research Council
Funding Amount
$597,675.00
Summary
Spinal cord injury has devastating effects on health and quality of life. Many of the major consequences of injury, such as chronic pain and loss of voluntary voiding, are "invisible" – i.e., they are not as visible as limitations of mobility. Our study aims to define the neurobiological changes that cause development of persistent pain after spinal cord injury and use pharmacological tools to attenuate the development of pain.
Our vestibular system provides us with the important sense of balance. When it fails we suffer debiltating bouts of vertigo and dizziness. A great deal is known about how balance signals are sent from the inner ear to our brains, but virtually nothing is known about the important signals the brain sends to the inner ear. In this study we will use a new perparation develped in our laboratory to examine how these essential brain signals control the function of our balance organs.
Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected areas of the cerebral cortex. Damage to these areas is a relatively common complication of preterm delivery and- or perinatal conditions including trauma and infection. The severity of both the short- and long-term effects of these lesions appears to be related to the time of the damage. The aim of this project is to investigate the way in which the multiple visual areas of the brain devel ....Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected areas of the cerebral cortex. Damage to these areas is a relatively common complication of preterm delivery and- or perinatal conditions including trauma and infection. The severity of both the short- and long-term effects of these lesions appears to be related to the time of the damage. The aim of this project is to investigate the way in which the multiple visual areas of the brain develop and become 'wired' together in the period following birth. We will also determine if there are mechanisms which allow alternate routes to be found for processing visual information while the brain is still establishing connections between its multiple areas. This will allow us to understand the anatomical and physiological bases of the deficits caused by early damage to the visual areas of the brain, and perhaps point to strategies that will lead to improved recovery of visual function.Read moreRead less
Current treatments for chronic pain are limited in their success. This emphasises the need for new insights into the basic mechanisms and nervous system circuitry underlying altered or chronic pain states. Work in animals and patients with chronic pain shows that certain brainstem centres communicate, via descending spinal cord pathways, with small nerve cells in the superficial dorsal horn (SDH) of the spinal cord. These SDH neurones receive and process pain-signalling information from the skin ....Current treatments for chronic pain are limited in their success. This emphasises the need for new insights into the basic mechanisms and nervous system circuitry underlying altered or chronic pain states. Work in animals and patients with chronic pain shows that certain brainstem centres communicate, via descending spinal cord pathways, with small nerve cells in the superficial dorsal horn (SDH) of the spinal cord. These SDH neurones receive and process pain-signalling information from the skin and internal organs, and receive inputs from descending pathways. This descending input can either inhibit or enhance the activity of SDH neurones and subsequent pain perception. Till now it has been difficult to directly examine how descending pain pathways influence the small SDH neurones in the spinal cord. A new approach, which has been developed in our laboratory, now allows us to record from these very small SDH neurones in the spinal cord of an intact deeply anaesthetized mouse. In addition, our technique allows us to examine the recorded SDH neurone s responses to functionally relevant stimuli (brushing or pinching the hindpaw) as well as its physiology and anatomy. This project will use our new techniques to examine the effects of activating descending brainstem pathways that alter the way painful stimuli are processed in the spinal cord. The effects of altered levels of inhibition in the spinal cord will also be studied by using mice with naturally occurring mutations in their inhibitory glycine receptors. We believe a more complete understanding of pain processing mechanisms will be achieved by examining the role of descending pathways in an intact animal preparation. Such data are essential for the development of drug therapies that can successfully target pain syndromes.Read moreRead less
Chronic pain and functional impairment following traumatic injury: an investigation into the impact of compensation status and experience. This project will enhance understanding of the impact of the psychosocial factors and the compensation process on recovery from traumatic injury. The project will generate new resources (screening and referral guidelines; educational materials) to improve decision making consistency, client experience, and recovery from road trauma.