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
An FMRI Analysis Of The Functional Organization Within The Brain Of Experimental Superficial And Deep Orofacial Pain
Funder
National Health and Medical Research Council
Funding Amount
$307,526.00
Summary
This project will investigate how the human brain processes a number of important aspects of human jaw muscle pain that are clinically relevant but poorly understood. For example, we do not understand why jaw muscle pain has such different behavioural effects to skin pain. Jaw muscle pain is associated with a significant emotional component not seen in with skin pains. Also, skin pain usually has a sharp or burning quality, is well-localized and is readily treated, while jaw muscle pain is a dee ....This project will investigate how the human brain processes a number of important aspects of human jaw muscle pain that are clinically relevant but poorly understood. For example, we do not understand why jaw muscle pain has such different behavioural effects to skin pain. Jaw muscle pain is associated with a significant emotional component not seen in with skin pains. Also, skin pain usually has a sharp or burning quality, is well-localized and is readily treated, while jaw muscle pain is a deep pain that has a dull, aching quality that may be referred to related sites of the face, head and neck. It is also not known why jaw muscle pain is more common in females in comparison to males. Chronic jaw muscle pain is a major symptom of patients with Temporomandibular Disorders, the most common form of non-dental orofacial pain and that involves pain in or about the jaw joint and-or jaw muscles, and often limitation of jaw movement. Chronic jaw muscle pain can have a severe effect on quality of life but its diagnosis and management is difficult. Despite the widespread prevalence of chronic orofacial pains, we have little information on the central processing of chronic human orofacial pain. This proposal will improve our fundamental understanding of how jaw muscle pain is processed in the brain. The way that the central nervous system processes and represents jaw muscle pain will help explain why these pains present differently in the clinic and should provide important information on the differences between females and males in the representation of jaw muscle pain. This information on the central processing of chronic orofacial pain is crucial to inform the direction of novel or specific management strategies. Our long-term goal is to improve the diagnosis and management of patients with Temporomandibular Disorders, and the present application represents a major new direction of research.Read moreRead less
Identification Of Heterogeneity In Vasodilator Function In Human And Rat Resistance Vessels: Potential Drug Targets?
Funder
National Health and Medical Research Council
Funding Amount
$595,330.00
Summary
The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not w ....The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not well understood. While current drugs for treating vascular disease either reduce vessel constriction or increase dilation, they are not specific for individual arteries; a situation that would allow us to control vascular diseases in a very specific manner. Recently, we have described differences between the ways that individual vessels are controlled. These changes relate to differences in the way that different vessels dilate. AIMS - To further understand normal blood vessel function and the changes that occur in blood vessels in cardiovascular disease, with a focus on the ways that blood vessels dilate in normal states and in obesity-related diseases, such as in hypertension and diabetes. - The eventual aim is to identify the specific ways that arteries function, so that artery-specific drug targets can be identified to treat disease-related changes in cardiovascular disease in a very specific manner. EXPECTED OUTCOMES This project will contribute to understanding blood vessel function in health and disease. The expected eventual outcome is the identification of the mechanisms that underlie the function of different arteries in different parts of the body, so that specific individual vessel function can be targeted to treat vascular disease. Additionally, this work will also verify the relevance of the diet-induced obesity animal model, in terms of the characteristics and causes of human obesity and related cardiovascular disease.Read moreRead less
Hydrostatic Pressure Distributions In Peri-pharyngeal Tissues : Impact On Upper Airway Patency
Funder
National Health and Medical Research Council
Funding Amount
$508,935.00
Summary
The obstructive sleep apnoea hypopnoea syndrome (OSAHS) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSAHS affects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in ~4% of men over the age of 45 years. In the proposed studies we will develop a computer model of the function of the throat during breathing. A particular focus of our mo ....The obstructive sleep apnoea hypopnoea syndrome (OSAHS) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSAHS affects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in ~4% of men over the age of 45 years. In the proposed studies we will develop a computer model of the function of the throat during breathing. A particular focus of our model will be the influence of the properties of the tissue that form the walls of the throat. Our goal is to construct a computer model that will be useful in identifying specific features of throat function that make people susceptble to the development of OSAHS. In this manner we hope to provide a tool that can be used to develop new approaches to the treatment and prevention of OSAHS.Read moreRead less
Glycine Transporters regulate the concentration of glycine in the spinal cord and brain. It has been suggested that elevating glycine levels in these regions may be useful in treating pain and schizophrenia. This project will provide the basis for the development of new glycine transport inhibitors that may be used to treat these conditions.
A Preclinical Model Of Relapse In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$573,515.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease. We also hope to identify markers that can be used to screen for patients at increased risk of relapse.
Mechanisms Of Escape From Progesterone-induced Suppression: Role In Normal And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Prematurity caused by preterm birth is the leading cause of death and disease among newborns in Australia. Here we will define how the length of pregnancy is determined by the opposing actions of progesterone, which maintains pregnancy, and prostaglandins, which induce labour. We will demonstrate the mechanism by which the actions of the two hormones are balanced in normal pregnancy and disrupted in preterm labour. We will show that preterm birth can be prevented by correcting the disorder.