Neural Mechanisms In Tactile, Kinaesthetic And Pain Sensation
Funder
National Health and Medical Research Council
Funding Amount
$644,113.00
Summary
Our knowledge of the world around us depends upon our sensory systems which provide a series of windows on the world, enabling the mind and brain to sample information about selected events through the energy forms that impinge upon us. Much of this sensing process takes place through our special sense systems such as the eye, the ear, and the taste and olfactory systems. However, other crucial sensory systems are more generalized throughout the body and are referred to as the somatic sensory sy ....Our knowledge of the world around us depends upon our sensory systems which provide a series of windows on the world, enabling the mind and brain to sample information about selected events through the energy forms that impinge upon us. Much of this sensing process takes place through our special sense systems such as the eye, the ear, and the taste and olfactory systems. However, other crucial sensory systems are more generalized throughout the body and are referred to as the somatic sensory systems. These include our senses of touch, temperature, pain and body position, the last of which is known as our kinaesthetic sense. Our research into the neural mechanisms in sensation and perception is concerned with the tactile, kinaesthetic and pain senses. Although many thousands of nerve fibres travel in the nerves arising from particular regions of the skin or from individual muscles or joints, the sensory nerve fibres that serve these forms of sensation fall into fewer than ten broad classes, made up of five major tactile classes, two or three major kinaesthetic classes, and two broad groups of fibres that mediate pain sensation. However, there is quite striking evidence that when single fibres of these different classes are activated in conscious human subjects, there are marked differences among the fibre classes in their capacity to generate a perceptual response. Under the new NH and MRC grant we propose to examine the transmission and processing of input signals from these fibre classes at the highest levels of the brain, in particular, within the cerebral cortex, in order to reveal the neural mechanisms responsible for their differential perceptual contributions. The proposed analysis will provide fundamental insights into the neural basis for perceptual recognition and will provide information that may be important for our eventual understanding of the disorders of sensory perception that characterize psychiatric conditions such as schizophreniaRead moreRead less
Mechanisms Of Mechanotransduction In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have ....Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have found that three genes are responsible for many aspects of mechanotransduction. Each gene is transcribed to produce a channel or pore in the membrane of sensory nerve fibres which responds to mechanical forces by allowing ions to enter and induce electrical signals. Our early findings in mice with disruption of individual genes indicate that a complex positive and negative interaction of these channels must underlie normal mechanotransduction. However, these channels must represent only a part of the transduction mechanism, with extracellular and intracellular anchors inevitably playing a major role. The identity of such anchoring proteins in mammals is currently emerging, and we are fortunate to have access to mice deficient in specific genes that will provide information about candidates for this role. Through our studies on mechanotransduction in the digestive system in parallel with our collaborators' studies on mechanotransduction in skin we shall not only identify the fundamental mechanisms of mammalian mechanotransduction, but also reveal which components of mechanotransducers are peculiar to the gut. Such peculiarities provide molecular targets for therapy of diseases in which alteration of mechanosensory signaling is itself an aim.Read moreRead less
Disorders of pain sensation due to nerve damage are common, debilitating and difficult to treat. Nerve damage often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. Pain is one of the commonest clinical problems, and yet it is often accepted or taken for granted. The outcome of this work will be an increased understanding of the way in which nerve injury leads to spontaneous pain and increased sensitiv ....Disorders of pain sensation due to nerve damage are common, debilitating and difficult to treat. Nerve damage often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. Pain is one of the commonest clinical problems, and yet it is often accepted or taken for granted. The outcome of this work will be an increased understanding of the way in which nerve injury leads to spontaneous pain and increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.Read moreRead less
Targeted Ablation Of Sensory Neurons And Glial Cells With A View To Relieving Neuropathic Pain.
Funder
National Health and Medical Research Council
Funding Amount
$280,910.00
Summary
In Australia more than half of chronic pain patients are diagnosed with neuropathic pain resulting from nerve injury. This type of pain persists long after injury has healed and is associated with spontaneous bursts of excruciating pain and altered sensory processing symptoms which can make even the light touch of clothing intolerable. Neuropathic pain is highly resistant to even the most intense and drastic pain treatments. Much research has been devoted to understanding neuropathic pain in ter ....In Australia more than half of chronic pain patients are diagnosed with neuropathic pain resulting from nerve injury. This type of pain persists long after injury has healed and is associated with spontaneous bursts of excruciating pain and altered sensory processing symptoms which can make even the light touch of clothing intolerable. Neuropathic pain is highly resistant to even the most intense and drastic pain treatments. Much research has been devoted to understanding neuropathic pain in terms of changes in nerve cell (neuron) structure, function and chemistry. Whilst we have learned a lot about how neurons contribute to neuropathic pain, it has since become clear that cells other than neurons (namely neuronal support cells called glia) also play a significant role in the production and continuation of pain after nerve injury. Thus, it may be that pain therapies which currently focus on stopping or minimising the changes in neurons after nerve injury are only doing half the job when it comes to relieving such pain. Targeted therapies aim to affect or kill particular groups of cells with the hope of further understanding their role in the disease progression or eliminating their contribution to the disease state to produce relief. This can be done using a toxin linked to a vehicle that only binds to a particular cell type and which, upon uptake, causes the cell to suicide. Targeting neurons and glia responsible for neuropathic pain may hold a key to relieving this pain state. This project aims to further understand the contributions of neurons and glia to the production of neuropathic pain and aims to determine the effectiveness of synergistic targeted therapies that kill both the neurons and glia responsible for neuropathic pain production. It is hoped that killing these cells will effectively remove their input to the production and continuation of neuropathic pain and may offer a new avenue for neuropathic pain treatment in the future.Read moreRead less
Peripheral Neuropathy And Pain: Role Of The Sphingosine Kinase-sphingosine 1-phosphate System
Funder
National Health and Medical Research Council
Funding Amount
$282,905.00
Summary
Understanding the neural mechanisms that generate pathological pain remains one of the essential goals for the development of effective treatments for pain, chronic pain with less side effects. Lipids are able to modulate pain perception. We will determine the role of a molecule named sphingosine 1-phosphate as a basis for the development of therapies for the treatment of neuropathic pain.
Neural Mechanisms Underlying Human Grasp And Manipulation
Funder
National Health and Medical Research Council
Funding Amount
$396,100.00
Summary
We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well ....We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well as in other neurological diseases such as neuropathies, nerve injuries, cerebral palsy and many others. The broad aim of this study is to investigate the poorly understood neural mechanisms that underlie sensorimotor control of hand function. We will target a specific aspect of manual dexterity that is crucial for the execution of common everyday tasks, like pouring liquid from a bottle, in which the digits are subjected to torsional loads. In order to maintain stable grasps, the motor control system must rapidly and automatically adjust the grip forces employed to meet the demands imposed by the changing torsion. This is only possible because of sensory feedback from the hand, a large component of which arises from the cutaneous mechanoreceptive afferent fibres. In the first two years we will use a combined approach of neural recording from peripheral nerves in anaesthetised monkeys and psychophysics experiments in normal humans to answer the general question: how does the population of cutaneous afferents provide precise feedback about torsion on the digits? In the third year we will perform key experiments in humans, using microneurography to record from their peripheral nerves. This will establish any differences between human and monkey mechanoreceptors.Read moreRead less
Sensory Neuronal Pathways From The Lower Genital Tract Of Females
Funder
National Health and Medical Research Council
Funding Amount
$397,224.00
Summary
Many women experience severe debilitating pain upon normally innocuous contact with their genitalia. The causes of this pain are unknown. Therefore, this project will use a suite of sophisticated microscopic and electrical recording techniques to identify the neural pathways that transmit sensation, including pain, from the female lower genital tract. Our new data will help create a rational basis for understanding and treating the physical basis of genital pain in women.
Interaction Of TRP Channels And Inflammatory Mediators: A Critical Role In Visceral Pain
Funder
National Health and Medical Research Council
Funding Amount
$308,747.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we feel, such as touch and pain. The function of these channels can be altered by substances released by the body during inflammation. Some TRP channels have specialized roles in signalling pain from the colon which can be enhanced during colonic inflammation. Understanding how TRP channels and inflammatory mediators function and interact is essential if we are to find treatments for colonic pain.
Examining The Role Of ASIC Channels In Pain Through The Development Of Subtype-specific ASIC Channel Modulators.
Funder
National Health and Medical Research Council
Funding Amount
$617,256.00
Summary
Acid sensing ion channels (ASICs) sense changes in acidity in the body. They are found throughout the body and may underlie nerve damage in stroke and some types of pain. ASICs also have many as yet unknown functions. A lack of selective tools to study ASICs is a major barrier to a complete understanding of what they do. This proposal aims to modify three animal toxins which block these receptors to make useful tools to study their function, in particular their role in sensing pain.