Interaction Between Symptoms Of Brainstem Disturbance, Sensory Disturbances And Pain In Migraine
Funder
National Health and Medical Research Council
Funding Amount
$165,509.00
Summary
Migraine affects about 18% of women and 6% of men across their lifespan and usually peaks during the most productive years of life. Although serious neurological effects of migraine are rare, some sufferers are left with permanent physical disability after attacks of migraine-related stroke. More common are debilitating side effects of medication, and the psychological and social disruption of experiencing recurrent attacks of migraine. Apart from the pain and distress experienced during migrain ....Migraine affects about 18% of women and 6% of men across their lifespan and usually peaks during the most productive years of life. Although serious neurological effects of migraine are rare, some sufferers are left with permanent physical disability after attacks of migraine-related stroke. More common are debilitating side effects of medication, and the psychological and social disruption of experiencing recurrent attacks of migraine. Apart from the pain and distress experienced during migraine, recurrent headaches are responsible for considerable health care costs and lost productivity. Thus, there are important economic and social reasons for developing new treatments, particularly treatments that reduce susceptibility to recurrent attacks. This project aims to investigate interactions among symptoms of migraine (head pain, nausea, and changes in facial blood flow), so that the sequence of symptom development can be studied systematically. We will induce motion sickness (which provokes nausea and many other symptoms of migraine), and then study the effects of head pain and strong sensory stimulation. We expect that migraine sufferers will report stronger symptoms and show greater physiological changes to these stimuli, either alone or in combination, than people who rarely suffer from headache. One of the most commonly recognized triggers of migraine is psychological stress. The aim of the second part of this project is to determine whether a substance released during stress (noradrenaline) heightens inflammation in scalp blood vessels, thus increasing the likelihood of migraine. We hope that this approach will help to identify the basis of the abnormality which increases susceptibility to migraine, so that it can be targeted for treatment.Read moreRead less
Mechanisms Controlling The Excitability Of Corneal Nociceptor Nerve Terminals
Funder
National Health and Medical Research Council
Funding Amount
$364,759.00
Summary
The project uses a new approach that allows, for the first time, electrical activity to be recorded and analysed from the very fine nerve endings of nerves whose activation results in painful sensations. Using this technique the mechanisms by which substances released in damaged and inflamed tissues lead to discharge of action potentials and the sensation of pain will be investigated. In particular the project investigates the role of a population of sodium ion selective pores (channels) that ar ....The project uses a new approach that allows, for the first time, electrical activity to be recorded and analysed from the very fine nerve endings of nerves whose activation results in painful sensations. Using this technique the mechanisms by which substances released in damaged and inflamed tissues lead to discharge of action potentials and the sensation of pain will be investigated. In particular the project investigates the role of a population of sodium ion selective pores (channels) that are uniquely expressed in pain sensing nerves. These channels have been hypothesised to play an important role in determining the behaviour of these nerves. In addition, the project investigates how some substances released in inflamed tissues sensitize pain sensing nerves, causing them to more readily discharge action potentials. This change is the major cause of pain associated with inflammatory diseases such as arthritis. In summary, the proposed project will provide new insight into how pain sensing nerves function. This knowledge is essential for the development of more effective strategies for treating pain resulting from inflamed and damaged tissue.Read moreRead less
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.
Substance P Antagonists As A Novel Therapeutic Intervention In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$318,267.00
Summary
Stroke is the major cause of disability in adults over 45 years of age in Australia. The economic and social cost of stroke is enormous with billions of dollars spent each year on the management and rehabilitation of stroke patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have now demonstrated that much of the morbidity following stroke is associated with the breakdown of the blood brain barrier, development of oedema, and ....Stroke is the major cause of disability in adults over 45 years of age in Australia. The economic and social cost of stroke is enormous with billions of dollars spent each year on the management and rehabilitation of stroke patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have now demonstrated that much of the morbidity following stroke is associated with the breakdown of the blood brain barrier, development of oedema, and subsequent brain damage in areas surrounding the central region of the stroke. These events develop over hours to days following the stroke and are known as secondary injury. This delayed progression of injury suggests that appropriate pharmacologic intervention can prevent, or at least attenuate, this secondary injury process with a resultant improvement in outcome. Nonetheless, few interventions are available that can limit this development. Our own recent studies have demonstrated that regions in brains which demonstrate the presence of stroke also exhibit signs of neurogenic inflammation, which has been associated with oedema formation, oxidative damage and cell death in other tissues. Although a number of neuropeptides have been implicated in this process, it is thought that substance P release is closely associated with these pathophysiological processes. Thus, inhibiting substance P binding may offer a novel therapeutic approach to attenuating oedema formation and the development of neurologic deficits following stroke. This proposal will utilise a combined biochemical, pharmacologic and behavioural approach to characterize the role of neurogenic inflammation in the development of oedema and neurologic deficits following stroke. Moreover, we will develop a novel pharmacotherapy that can potentially be used in the treatment of clinical stroke.Read moreRead less
A Novel Sensory Nerve Stimulator To Improve Neuropathy In Patients With Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$407,924.00
Summary
We have developed a painless, self-applied, cheap, battery powered electrical stimulation treatment that improves sensory nerve function in some people with diabetic peripheral neuropathy. We have tested this technique in laboratory animals and in people with diabetes and have shown it is effective in some. We now propose to test this technique in a large sample of people similar to the participants in the successful group of our pilot study - 55-65 year old people with diabetes of shorter durat ....We have developed a painless, self-applied, cheap, battery powered electrical stimulation treatment that improves sensory nerve function in some people with diabetic peripheral neuropathy. We have tested this technique in laboratory animals and in people with diabetes and have shown it is effective in some. We now propose to test this technique in a large sample of people similar to the participants in the successful group of our pilot study - 55-65 year old people with diabetes of shorter duration. In addition, older people up to 75 years of age, with up to 10 years duration of diabetes will be included separately. If successful, the electrical stimulation could improve sensation leading to fewer ulcerations and amputations. Much suffering and expense would be avoided. - The magnitude of reduction in suffering and expense can be judged from the fact that people with diabetes have 15 times the risk of amputation as do people without diabetes. In Australia half of non-traumatic amputations are done to people with diabetes. Foot ulcers precede amputations in most cases, and in themselves cause much suffering and expense. Australia needs to act on this now because, if current trends continue, the number of people with diabetes will increase as the population ages. -The number of people aged over 65 will increase from around 2.3 million at present to over 6 million in the next half century. The increase in those over 85 will be even more marked with numbers increasing four fold to over one million people. Diabetes affects approximately 23% of people aged 75 or older.Read moreRead less
Novel Substance P Receptors On Autonomic And Sensory Neurons Regulating The Viscera
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
Potentially harmful stimulation of the skin or the internal organs activates sensory nerves that send signals to the brain. These events often are perceived as painful. One chemical messenger transmitting these signals first to the spinal cord, and then to the brain, is a neuropeptide called substance P. During many chronic inflammatory conditions, such as inflammation of the bowel, these signalling pathways are sensitised so that stimuli that previously were not painful now are perceived as pai ....Potentially harmful stimulation of the skin or the internal organs activates sensory nerves that send signals to the brain. These events often are perceived as painful. One chemical messenger transmitting these signals first to the spinal cord, and then to the brain, is a neuropeptide called substance P. During many chronic inflammatory conditions, such as inflammation of the bowel, these signalling pathways are sensitised so that stimuli that previously were not painful now are perceived as painful. This sensitisation has several different causes. One contributing factor seems to be related to a change in the receptor molecules that recognise substance P. Last year we discovered a new type of receptor for substance P, that is prominent in the nerve pathways between the gut and the spinal cord. This novel receptor has important characteristics that are different from the classical substance P receptor. However, we are still largely ignorant about how substance P interacts with these new receptors to modify the activity of nerve cells in sensory pathways. Indeed, we propose that these new receptors are likely to make a significant contribution to the sensitisation that occurs in inflammation. We will use a combination of sophisticated cellular and molecular techniques to study the way in which substance P acts on these novel receptors in nerves regulating the visceral organs. Our results are likely to make a significant contribution to the development and interpretation of rational new therapies for treating chronic diseases of the gastrointestinal tract, such as inflammatory bowel disease (IBD). Our studies will reveal signalling mechanisms that also are likely to be used by substance P more widely in the nervous system, that are relevant to other inflammatory conditions like arthritis, and even some forms of depression.Read moreRead less
Communication Connect: Improving Long Term Communication And Mental Health Outcomes Following Stroke And Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$1,809,756.00
Summary
The 250,000 Australians living in the community with communication disability caused by stroke and traumatic brain injury experience unacceptably high rates of depression, anxiety, inactivity and social isolation. Their carers experience high levels of burden, and they struggle to access health and community services. We aim to develop and test a program of community and self-managed care, aimed at reversing these negative impacts and reducing reliance on high cost health care services.
Characterisation Of Substance P Antagonists As A Novel Therapeutic Intervention For Use In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
Traumatic brain injury (TBI) is responsible for more deaths in Australians under 45 years of age than any other cause. The economic and social cost of head injury to the community is enormous with billions of dollars spent each year on the management and rehabilitation of trauma patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have demonstrated that much of the morbidity following TBI is associated with the development of ....Traumatic brain injury (TBI) is responsible for more deaths in Australians under 45 years of age than any other cause. The economic and social cost of head injury to the community is enormous with billions of dollars spent each year on the management and rehabilitation of trauma patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have demonstrated that much of the morbidity following TBI is associated with the development of a secondary injury process that occurs between hours to days after the insult. This delayed progression of injury suggests that appropriate pharmacologic intervention can prevent, or at least attenuate, this secondary injury process with a resultant improvement in outcome. Over the past 15 years, a number of groups, including ours, have been investigating the secondary mechanisms associated with the development of functional deficits after TBI. Our previous studies have demonstrated that decline in brain free magnesium is associated with functional deficits after experimental brain injury, and that magnesium administration after injury can improve outcome. Magnesium is now on clinical trial as a pharmacologic intervention. Recent studies have suggested that magnesium decline facilitates neurogenic inflammation, which has been associated with oedema formation, oxidative damage and cell death. Although a number of neuropeptides have been implicated in this process, it is thought that substance P release is closely associated with these pathophysiological processes. Therefore, inhibiting neuropeptide release, or inhibiting substance P binding, may offer a novel therapeutic approach for the attenuation of oedema and development of neurologic deficits after TBI. This proposal will use a combined biochemical, pharmacologic and behavioural approach to characterise the role of neuropeptides in brain trauma, and attempt to develop a novel therapy for use in clinical trauma.Read moreRead less
Non-invasive Electrical Nerve Stimulation To Improve Healing Of Chronic Venous Leg Ulcers
Funder
National Health and Medical Research Council
Funding Amount
$206,210.00
Summary
Chronic venous leg ulcers are common in the elderly. They often last for many months or years, causing much suffering and expense (currently around $600,000,000 per year in Australia). As more and more Australians live into advanced age, more and more people will be troubled by leg ulcers, particularly as the likelihood of having a leg ulcer increases markedly in the very old. We have developed a painless, cheap treatment that improves wound healing. The treatment consists of electrical stimulat ....Chronic venous leg ulcers are common in the elderly. They often last for many months or years, causing much suffering and expense (currently around $600,000,000 per year in Australia). As more and more Australians live into advanced age, more and more people will be troubled by leg ulcers, particularly as the likelihood of having a leg ulcer increases markedly in the very old. We have developed a painless, cheap treatment that improves wound healing. The treatment consists of electrical stimulation of nerves that supply the wound. Low frequency current is passed through the skin from small battery powered stimulators. We have tested this technique in laboratory animals and in just a few older people with diabetes and have shown it is remarkably effective. We now plan to test this technique properly in a large study in older adults. If successful, the electrical stimulation could result in healing of wounds in relatively few weeks that otherwise would not heal for many months. Much suffering and expense would be avoided. As people age, nerve function deteriotes. Another part of the project will explore whether electrical nerve stimulation can improve damaged nerves themselves. This will provide interesting scientific insight about nerve repair and could lead to treatments for peripheral neuropathy that occurs in diabetes and other medical conditions. Australia needs to act on this now because the number of people aged over 65 will increase from around 2.3 million at present to over 6 million in the next half century. The increase in those over 85 will be even more marked with numbers increasing four fold to over one million people. Many of these people will experience severe impairment of their quality of life from leg ulcers that could be avoided, or at least minimized if a successful treatment is developed and made available to them. Similarly, much unnecessary expense could be avoided.Read moreRead less