SENSORIMOTOR AND AUTONOMIC DYSREGULATION IN HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES
Funder
National Health and Medical Research Council
Funding Amount
$50,406.00
Summary
Specific genetic mutations can lead to widespread changes in the body. Here we are looking at the congenital Hereditary and Sensory Autonomic Neuropathies, the most common of which primarily affects Eastern European Jews. Affected individuals have difficulty walking and controlling their blood pressure, and also have an indifference to pain. This series of experiments aims to increase our understanding of the underlying neurophysiological disturbances.
Mechanisms Underlying Disordered Skin Blood Flow Following Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$408,000.00
Summary
Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead to similar problems. This project is directed at understanding ....Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead to similar problems. This project is directed at understanding the role of the nerve supply to blood vessels in the skin in these disorders. The experiments will be conducted in skin blood vessels of rats with various forms of nerve lesion that will mimic these conditions in patients. We will use our knowledge of the structure and behaviour of nerve-blood vessel connections to analyse the changes in the properties of vascular smooth muscle and relate it to the state of the innervation. Skin arteries normally receive two types of nerve - sympathetic (which release noradrenaline) and afferent ( which release peptides) - that have opposing actions on the vessel (constriction and dilation respectively). We hypothesize that removal of part or all of the innervation changes the contractile mechanism of the smooth muscle in the wall of the vessel so that it becomes much more sensitive to calcium ions and produces larger and more prolonged contractions. We will combine electrophysiology and contraction studies with immunohistochemistry and biochemical analysis to define the relation between the nerve deficit and the vascular responses. The aim is to identify appropriate drug targets for which local application in the affected region can alleviate the symptoms without causing widespread side effects.Read moreRead less
Involvement Of Adrenergic Receptors In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$345,473.00
Summary
After nerve or tissue injury including burns, some people will suffer from a condition called neuropathic pain. This is a condition where chronic pain is endured, often totally unrelated to the initial injury or induced by events that would normally not be painful. Our project will determine whether this abnormal pain response is due to an abnormal communication between the nerves that carry pain signals (sensory nerves) and nerves that form part of the sympathetic nervous system, which is part ....After nerve or tissue injury including burns, some people will suffer from a condition called neuropathic pain. This is a condition where chronic pain is endured, often totally unrelated to the initial injury or induced by events that would normally not be painful. Our project will determine whether this abnormal pain response is due to an abnormal communication between the nerves that carry pain signals (sensory nerves) and nerves that form part of the sympathetic nervous system, which is part of autonomic (or involuntary) nervous system. We believe that this abnormal communication is due to an increase in the expression of special receptors called adrenergic receptors, on the sensory nerves. Our project will look at these receptors in the skin of animals that have had pain conditions induced, and also in skin samples from patients who suffer from neuropathic pain that can be classified as sensitive to sympathetic stimulation. By better understanding how neuropathic pain is derived, we can open the door to novel treatment approaches in these difficult to treat conditions.Read moreRead less
Peripheral and central mechanisms of sensory coding and integration. The research described in this proposal seeks to provide generic answers to fundamental questions about sensory processes, the nature of perceptual experience, and how these are subserved by the nervous system. The study of inter-sensory interactions in perception has the potential to be incorporated into the development of virtual reality-type computer-based technologies. The neurophysiology research will provide basic informa ....Peripheral and central mechanisms of sensory coding and integration. The research described in this proposal seeks to provide generic answers to fundamental questions about sensory processes, the nature of perceptual experience, and how these are subserved by the nervous system. The study of inter-sensory interactions in perception has the potential to be incorporated into the development of virtual reality-type computer-based technologies. The neurophysiology research will provide basic information that has the potential to deepen our understanding, and even enhance possible treatment, of neurological conditions that involve sensory systems.Read moreRead less
The Effects Of Tonic Muscle Pain On The Sympathetic And Somatic Motor Systems In Human Subjects
Funder
National Health and Medical Research Council
Funding Amount
$462,948.00
Summary
The main objective of this proposal is to reveal the effects of nociceptive reflexes in humans, and thus identify their functional and clinical implications. By performing invasive recordings from the nerves that control blood vessels and muscles in healthy volunteers subjected to long-lasting (~1 hour) experimental pain, this work will increase our understanding of the adaptive changes that pain induces and improve treatments to prevent pain from becoming chronic.
Decrypting The Excitation Contraction Coupling Machinery In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$914,869.00
Summary
Skeletal muscle function is dependent upon the fine control of calcium levels. When communication of key proteins in muscle are compromised, calcium levels are uncontrolled leading to severe disabilities. The molecular pathways that control signalling between key muscle proteins is currently unknown and shedding light on this topic will aid in the discovery of therapies for muscle-associated disabilities in disease and with aging.
Promoting Regrowth Of Nerve Fibres Into The Epidermis During Diabetic Neuropathy By LRP Agonists
Funder
National Health and Medical Research Council
Funding Amount
$427,102.00
Summary
Nerve damage can develop post injury or disease and is often very debilitating, slow to heal and can cause increased pain. Our work aims to examine a new class of molecules that we show can activate selected fat-receptors on nerve cells to guide the growth of regenerating nerves. We will determine how these receptors function with the aim of developing a novel class of therapeutics directed at healing nerve damage.
The role of spike patterning in shaping human perception of tactile stimuli. Every touch sensation from our fingertips is conveyed to the brain through the nerves by means of electrical impulses similar to any digital device. Using unique technology developed in our lab we can intercept this neural communication and insert our own messages to test how these signals are interpreted and converted into perceptual experiences. We aim to reveal the rules by which timing of neural signal patterns shap ....The role of spike patterning in shaping human perception of tactile stimuli. Every touch sensation from our fingertips is conveyed to the brain through the nerves by means of electrical impulses similar to any digital device. Using unique technology developed in our lab we can intercept this neural communication and insert our own messages to test how these signals are interpreted and converted into perceptual experiences. We aim to reveal the rules by which timing of neural signal patterns shapes the perception of touch - specifically intensity and frequency of vibration. By recording signals from neurons and by testing human perception, we will learn about neural processing mechanisms. The new knowledge generated about sensory coding will be essential for rendering a virtual sense of touch.Read moreRead less
The encoding of friction by tactile mechanoreceptors - the key to fingertip force control during dexterous object manipulation by humans. Unmatched human ability to control the hand so that brittle objects are gently held without slipping, or being crushed by excessive force rely on sophisticated tactile sense in the fingertips. This project will record and analyse signals which human nerves are sending from fingertip receptors to the brain centres controlling hand actions.
Sensory mechanisms underlying human dexterity in object manipulation. This project aims to understand the sensory mechanisms and biomechanics underlying sensory encoding. Tactile sensory information is crucial for controlling grip forces so that delicate objects are held without slipping, or being crushed by excessive force. This project will record signals from single human tactile receptors using microneurography. By modelling the neural data with skin biomechanical events, this project aims t ....Sensory mechanisms underlying human dexterity in object manipulation. This project aims to understand the sensory mechanisms and biomechanics underlying sensory encoding. Tactile sensory information is crucial for controlling grip forces so that delicate objects are held without slipping, or being crushed by excessive force. This project will record signals from single human tactile receptors using microneurography. By modelling the neural data with skin biomechanical events, this project aims to reveal sensory mechanisms underlying the human ability to manipulate objects and use tools. This research could lead to next generation sensory-controlled prosthetics and robotic manipulators.Read moreRead less