Does The Complement System Contribute To Neuropathic Pain?
Funder
National Health and Medical Research Council
Funding Amount
$262,958.00
Summary
Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes ....Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes to neuropathic pain. We have evidence that inflammatory responses play a key role in initiating neuropathic pain. Other evidence suggests that the immune system contributes to neurological diseases and accompanying pain (e.g. Guillain-Barr syndrome and multiple sclerosis). We plan to test the idea that a component of the immune system known as the complement pathway contributes to the development of neuropathic pain following peripheral nerve injury. The outcome of this work will be a better understanding of the way in which nerve injury leads to chronic disorders of pain, including increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.Read moreRead less
Understanding The Role Of Regulatory T Cells In Chronic Pain Following Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$587,046.00
Summary
Neuropathic pain is a debilitating condition of chronic pain that develops after damage to the nervous system, and lacks an effective treatment. This project focuses on the novel hypothesis that the immunosupressive regulatory T cells and their mediators play a critical role in controlling neuroinflammation and pain hypersensitivity following peripheral nerve injury. This study promises to enhance our understanding of the neuroimmune activation in neuropathic pain and offers novel approaches for ....Neuropathic pain is a debilitating condition of chronic pain that develops after damage to the nervous system, and lacks an effective treatment. This project focuses on the novel hypothesis that the immunosupressive regulatory T cells and their mediators play a critical role in controlling neuroinflammation and pain hypersensitivity following peripheral nerve injury. This study promises to enhance our understanding of the neuroimmune activation in neuropathic pain and offers novel approaches for pain management.Read moreRead less
Deciphering The Mechanisms For Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$496,321.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries The results of these experiments will provide important information on the the initial growth and targeting of these nerve cells which may have implications for regeneration of these as well as other nerve cells.Read moreRead less
Signals And Noise: A Study Of The Neurocognitive Mechanisms Underpinning Habituation To Noise In Normal And Damaged Hearing
Funder
National Health and Medical Research Council
Funding Amount
$408,938.00
Summary
McLachlan and Wilson recently published the first model of hearing that combines brain structure with function. This model postulates that recognition mechanisms initiate first, and then regulate the processing of other features. This project will investigate whether recognition mechanisms enable the auditory system to adapt to repetitive (background) noise by predicting and inhibiting responses to these sounds, and any changes in these mechanisms that may accompany hearing damage and tinnitus.
Peripheral and central mechanisms of sensory coding and integration. The research described in this proposal seeks to provide generic answers to fundamental questions about sensory processes, the nature of perceptual experience, and how these are subserved by the nervous system. The study of inter-sensory interactions in perception has the potential to be incorporated into the development of virtual reality-type computer-based technologies. The neurophysiology research will provide basic informa ....Peripheral and central mechanisms of sensory coding and integration. The research described in this proposal seeks to provide generic answers to fundamental questions about sensory processes, the nature of perceptual experience, and how these are subserved by the nervous system. The study of inter-sensory interactions in perception has the potential to be incorporated into the development of virtual reality-type computer-based technologies. The neurophysiology research will provide basic information that has the potential to deepen our understanding, and even enhance possible treatment, of neurological conditions that involve sensory systems.Read moreRead less
Plasticity of gastrointestinal vagal afferents. The aim of this project is to identify how leptin modulates specific subtypes of vagal afferent within the gut and the plasticity of this system under different dietary conditions. This proposed project will substantially increase understanding of the interactions between leptin, known to influence food intake, and vagal afferent satiety signals. It will also increase understanding of how these interactions alter in obesity and ultimately provide t ....Plasticity of gastrointestinal vagal afferents. The aim of this project is to identify how leptin modulates specific subtypes of vagal afferent within the gut and the plasticity of this system under different dietary conditions. This proposed project will substantially increase understanding of the interactions between leptin, known to influence food intake, and vagal afferent satiety signals. It will also increase understanding of how these interactions alter in obesity and ultimately provide targets and/or concepts for the pharmacotherapy of obesity.Read moreRead less
Central pathways regulating visceral pain. This project aims to investigate the neural pathways within the spinal cord and brain processing colorectal pain perception. The project aims to identify the spinal cord neurons relaying colorectal signalling into the brain and the influence of descending modulation from the brainstem upon these pathways. The outcomes will greatly benefit fundamental understanding of the central pathways processing visceral pain.
The Role Of Corticothalamic Feedback On The Response Dynamics Of Thalamic Neurons
Funder
National Health and Medical Research Council
Funding Amount
$351,852.00
Summary
A fundamental question in neuroscience is how the brain selectively processes sensory information to generate a reliable representation of the world. Positioned in the centre of the brain, the thalamus plays a key role in sensory processing. This project investigates how the interaction between thalamus and cortex shapes the selection and gating of sensory information. This is a fundamental question in basic neuroscience with the potential to increase our knowledge about attentional deficits.
The Role Of Dopamine And Other Neuromodulators As Light Signals In The Inner Retina: A Link To Night Blindness Disorders
Funder
National Health and Medical Research Council
Funding Amount
$250,250.00
Summary
Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-ligh ....Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-light switch can have fatal consequences. Night blindness is a symptom characterised by reduced vision in the dark and slow adaptation to dim light. Some congenital night blindness disorders are caused by mutations in the photoreceptor calcium channels which mediate signal transmission. Additionally, patients treated with neuroleptics, a group of drugs which affect the dopaminergic system, suffer night vision disorders. Dopamine acts as a light signal in the retina. AII amacrine cells are pivotal neurones for night vision segregating two channels (ON and OFF) which convey visual information. AII cells are modulated by dopamine and thus, represent interesting targets to study the role of dopamine in the dark-light switch. Much is know about the action of dopamine on transmission of ON signals channelled by AII cells. However, its action on the OFF channel is largely unknown. We believe that some night vision disorders originate by imbalance in the dopaminergic system in the retina and its effects on AII cells. We will test our hypothesis by studying the modulatory effect of dopamine on calcium dependent signal transmission between AII cells and their partners in the OFF channel. Our hypothesis will be further tested by using animal models in which dopamine receptor function is altered. The results of these studies will provide us with an invaluable model to understand the physiological basis of the dark-light switch and of the role of dopamine in night vision disorders.Read moreRead less
Muller Cell Reactivity During Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
Diabetes is the leading cause of blindness in the working population. In some patients with diabetes, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an increase in growth factors from cells within the retina called Muller cells. Muller cells are vital for the normal function of ....Diabetes is the leading cause of blindness in the working population. In some patients with diabetes, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an increase in growth factors from cells within the retina called Muller cells. Muller cells are vital for the normal function of the retina and are known to be abnormal late in diabetes. They may also be dysfunctional early in diabetes and could play a significant role in causing the early changes seen in diabetes. Therefore a good understanding of how Muller cells change and the time at which they change is vitally important to gain a better understanding of the defects that are associated with diabetes. Furthermore, an understanding of the basic underlying cellular changes that occur in dibaetes will aid the development of more specific therapeutic agents in the future.Read moreRead less