Reconsideration Of The Mechanisms Underlying Movement Changes With Pain
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
Pain changes the way we move. Although undisputed, there is a surprising lack of agreement regarding the underlying mechanisms. This project involves an innovative mix of neurophysiological methods to investigate how the drive to muscle cells from the nervous system is altered during pain. We aim to resolve the perplexing problem of how pain changes our ability to activate muscle. Our findings are likely to provide a clear understanding of the underlying mechanisms and guide rehabilitation.
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.
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
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.
DHPR ? Subunit Binding To A Variably Spliced Region Of RyR1: A Role In EC Coupling And Myotonic Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
We have uncovered a communication pathway between two ion channel molecules in muscle cells that underlies human movement. The pathway is critical in normal mobility and is disrupted in myotonic dystrophy. We will study the molecular components of this pathway to understand normal body function and abnormal function in mytotonic dystrophy. The work will facilitate the design of drugs to relieve the mytotonic dystrophy myopathy and form new and much needed class of specific muscle relaxants.
Can Persistent Bladder Pain Be Treated By Targeting TRPA1 Expressing Nociceptors?
Funder
National Health and Medical Research Council
Funding Amount
$687,730.00
Summary
Persistent visceral pain is extremely difficult to treat and manage. To solve this problem we need to understand how pain nerves in internal organs differ from those in skin and muscle. We have discovered a pain-detecting molecule TRPA1 in bladder sensory nerves. We aim to show how bladder inflammation changes the function of these bladder pain detectors and test a new way of selectively anesthetising them. We also will use a new technique to study how the bladder lining detects pain.
Mechanism And Treatment Of Sympathetically Maintained Pain
Funder
National Health and Medical Research Council
Funding Amount
$482,962.00
Summary
This project investigates a crucial but neglected element in the mechanism of chronic pain that develops after nerve and tissue injury. In particular, our aim is to establish whether expression of a chemical target of the neurotransmitter noradrenaline increases in the painful skin of affected patients, and whether medication that blocks this target alleviates inflammation and pain. If so, this may open up new avenues for treatment for previously intractable pain syndromes.
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
What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated with disease, for example, arthritis. Our laboratory has shown that a particular protein is a key mediator of inflammatory pain. The project is to understand how this particular protein promotes pain, including how it sensitzes neurons.