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.
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.
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
Extraction Of Key Features Of Natural Speech By Ventral Cochlear Nucleus Neurons
Funder
National Health and Medical Research Council
Funding Amount
$225,330.00
Summary
Little is known about how speech is processed and transformed by the central auditory pathway, and how the critical temporal and spectral features that identify a speech sound segment (a phoneme) are extracted. To date, most studies have approached this issue by using synthetic speech and examined the responses of the peripheral auditory nerve only. The aim of this study is to examine how important features of naturally-spoken speech are encoded by the cochlear nucleus (CN) - the first station i ....Little is known about how speech is processed and transformed by the central auditory pathway, and how the critical temporal and spectral features that identify a speech sound segment (a phoneme) are extracted. To date, most studies have approached this issue by using synthetic speech and examined the responses of the peripheral auditory nerve only. The aim of this study is to examine how important features of naturally-spoken speech are encoded by the cochlear nucleus (CN) - the first station in the auditory pathway located in the brainstem. The CN is a complex of different cell types that have the capacity to transmit, transform, and encode complex acoustic information in different ways. The proposed experiments involve recording the bioelectrical signal from single CN cells in anaesthetised rats while presenting naturally-spoken syllables, both in quiet and in the presence of noise. It is important to examine what happens to the neural responses in the latter condition, because all animals must cope with the problem of extracting important signals from background noise. While noise clearly interferes with the perception of another sound, the auditory system is in fact quite good at extracting signals in the presence of noise. This is well demonstrated by our ability to understand speech in the presence of quite high noise levels. This ability is severely degraded in the hearing impaired. Thus, one of the aims of this study is to examine the mechanisms and limits of the CN's ability to encode speech in a noisy background. A greater understanding of the mechanisms the nervous system uses to extract critical features of speech will not only build on our knowledge of auditory brainstem processes, but may also provide clues to improving processing strategies for cochlear implants.Read moreRead less
Transient Receptor Potential Channels (TRPs) As Transducers And Targets In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$669,130.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we perceive, such as heat, cold, touch and pain. Some TRP channels are specialized to signal pain from visceral organs, which we must investigate if we are to find treatments for visceral pain, which are currently lacking.