Obesity is a looming health crisis for Australians; it increases the chances of many serious diseases including diabetes, cancer, stroke and heart disease. Obesity occurs when the amount of energy consumed in food is greater than the energy used over an extended period. Because human beings usually get most of their food in a few meals each day, the size of those meals is very important. Deciding when to stop eating can exert a powerful control on energy intake. It is well known that nutrients r ....Obesity is a looming health crisis for Australians; it increases the chances of many serious diseases including diabetes, cancer, stroke and heart disease. Obesity occurs when the amount of energy consumed in food is greater than the energy used over an extended period. Because human beings usually get most of their food in a few meals each day, the size of those meals is very important. Deciding when to stop eating can exert a powerful control on energy intake. It is well known that nutrients reaching the gut cause the release of hormones from cells in the lining of the stomach and intestine. These hormones tell the brain when enough food has been consumed. It used to be thought that the hormones travelled in the blood stream to affect the brain directly. Recently, it has become clear that much of their effect is actually carried by sensory neurons with endings in the lining of the gut. The hormones have a powerful effect the sensory nerve fibres which then send electrical signals in nerve fibres running in the vagus nerve to the brain. Here they make connections which eventually influence the centres that control feeding. There is much to understand about how hormones affect the sensory nerve endings in the wall of the gut, whether all nerve fibres are affected the same way and what sort of information is conveyed to the brain. This project will use electrophysiological methods to identify which nerve fibres are activated by hormones, whether different hormones affect different nerve fibres, which nutrients activate particular nerve fibres and whether nerve fibres make selective contacts with particular hormone-releasing cells. These questions are important for understanding how we normally stop feeding and how drugs might be designed to cause feelings of fullness earlier in each meal.Read moreRead less
The Role Of Gastric Vagal Afferents In The Food Intake Reducing Effect Of Oestradiol
Funder
National Health and Medical Research Council
Funding Amount
$317,739.00
Summary
Regulation of food intake is paramount for maintaining health. Nerves from the stomach serve as important regulators of food intake. These nerves can be modulated by chemical substances; however the importance of this modulation is not well defined. The sex steroid, oestradiol, has potent food intake reducing effects, but the mechanism for this is poorly understood. Thus, this fellowship will examine the role that oestradiol has in regulating food intake by acting on nerves within the stomach.
Diabetic neuropathy causes severe disability, with pain, loss of sensation and weakness. The current project will assess the utility of a new testing method, known as nerve excitability assessment, as a method of detecting early changes in nerve function in diabetic patients. If this technique proves useful in detecting early nerve damage, it will assist in the development of therapeutic and preventative treatments for neuropathy in diabetic patients.
Long-term Nerve Damage In Cancer Survivors: Identification Of Risk Factors And Optimal Assessment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$850,172.00
Summary
Nerve damage following chemotherapy treatment leads to early treatment cessation and long-lasting disability, developing with commonly used chemotherapies. There is a critical need to understand the mechanisms, optimize clinical assessment and develop interventions to prevent nerve damage. This project is designed to detect the impact of long-term nerve damage in cancer survivors and develop a risk profile based on clinical, neurophysiological and genetic factors.
The Biophysical Basis Of HCN Channels In Human Peripheral Nerve
Funder
National Health and Medical Research Council
Funding Amount
$50,315.00
Summary
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play an important role as pacemakers in the cardiac and nervous systems. HCN channel dysfunction is implicated in a number of disorders including neuropathic pain and epilepsy. My aim is to determine the kinetics and voltage dependence of HCN channels in human peripheral nerve in vivo. Understanding these channels is a prerequisite to the development of safe targeted therapies against neuropathic 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
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