Thalamic Neuroplasticity And Pain Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$299,520.00
Summary
Pain is a major problem for people with spinal cord injuries and is common, severe and difficult to treat. There is increasing evidence to suggest that pain may be linked to specific changes in some brain regions following a spinal cord injury. Several possible brain changes have been suggested but not investigated fully and have different implications for treatment. This project aims to characterise these brain changes with the purpose of developing novel effective and targeted treatments.
INVESTIGATIONS ON THE REGULATION OF INTERVERTEBRAL DISC CELL MATRIX METALLOPROTEINASES
Funder
National Health and Medical Research Council
Funding Amount
$331,320.00
Summary
Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem w ....Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem will increase in severity over the next few decades. American Bureau of Census data indicate that between 1990 to 2010 the number of people >45 years will increase from 82 to 124 million, the number of elderly in emerging countries will also increase between 200 to 400% in the next 30 years. In the United States, back-pain is the second most common reason that people visit a physician and medical conditions related to back-pain account for more hospitalisations than any other musculoskeletal disorder. Despite its high incidence, associated problems of incapacity and economic implications, costed at $100 million per annum in Australia in 1992, and US$100 billion globally in 1999-2000 (Dorland Data Networks, PA, USA) the causes of low back-pain are still poorly understood. Disc disease is responsible for 23-40% of all cases of low back-pain. The management of discogenic low back-pain is currently empirical, directed either toward life-style changes to minimise symptomatology or to surgical resection or spinal arthrodesis to restrict articulation. Based on our recent findings and those of colleagues over the last 16 years, it is our strong conviction that it should be possible with a better understanding of disease mechanisms and with the use of modern technologies to inhibit, reverse or ideally prevent disc degeneration. Without such basic research there will be no scientific foundation upon which prospective therapies may be based.Read moreRead less
Chronic neck pain is difficult to treat and can result in a complex set of symptoms, including dizziness, disturbed vision, and exaggerated pain responses in the upper torso and arms. Thus, there is a need to develop new treatments for this debilitating condition. This project will study how damage to structures in the neck alters the excitability of nerve cells in the upper cervical spinal cord. The results will provide a foundation for development of therapies to treat chronic neck pain.
Excitatory Interneurons: A Sensory Amplifier For Pathological Pain
Funder
National Health and Medical Research Council
Funding Amount
$649,848.00
Summary
Changes to the nervous system during pathological pain remain poorly understood. This poses a barrier to new and more effective pain therapies. We have recently shown that a population of excitatory nerve cells, which express a protein called calretinin, form an amplifier network within the spinal cord that enhances pain signalling. This application will determine how calretinin-positive nerve cells contribute to pathological pain and can subsequently be targeted to provide pain relief.
The Next Generation Of Biomaterials; In Vivo Assessment Of Lumbar Spinal Fusion Biodegradable Interbody Cages
Funder
National Health and Medical Research Council
Funding Amount
$85,932.00
Summary
Back pain represents one of the major health and economic problems facing the western world. Surgery is an inevitable outcome for many sufferers and involves the implantation of metallic rods screws, plates or cages. Biodegradable implants have theoretical advantages, but until now no material has existed that can sustain he rigours of implantation into a load bearing site. We have developed such a material which will lead to improvements in the treatment of many orthopaedic conditions.
Chronic pain is a debilitating syndrome caused by damage to tissue and the nervous system, arising from trauma and disease. It is poorly served by current drugs. To identify novel more effective therapies we propose to examine the mechanisms underlying this syndrome. We have identified a novel protein which is involved in synaptic plasticity. We will examine its role the development of chronic pain at the cellular level and how it might be exploited for the treatment of chronic pain.
Identifying The Neural Signature Of Persistent Pain
Funder
National Health and Medical Research Council
Funding Amount
$547,094.00
Summary
Chronic pain affects over 20% of Australians. Despite its high prevalence, it is relativly resistant to current treatment regimes and part of the reason behind our inadequate ability to provide satisfactory pain relief is due to our limited understanding of the pathophysiology that underlies this condition. This proposal will develop a novel understanding of the central neuroplastic changes associated with chronic pain and the role that these changes play in the maintenance of these conditions.
I am a neuroscientist who is fascinated by the ways in which peripheral and spinal neurons respond to environmental changes. By understanding these responses, I hope to develop new ways to treat neural conditions caused by injury, endocrine disturbances and inflammation.
The Role Of Presynaptic Inhibition In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$466,045.00
Summary
Inhibitory nerve cells in the spinal cord are thought to play an important role in governing the interaction between painful and non-painful stimuli. Defects in this process underlie allodynia, an important symptom of neuropathic pain. We will use recent advances in genetic techniques (optogenetics) to manipulate and study how inhibitory nerve cells separate touch and pain signalling in the spinal cord of normal and neuropathic animals.
Current treatments for chronic pain are limited in their success. This emphasises the need for new insights into the basic mechanisms and nervous system circuitry underlying altered or chronic pain states. Work in animals and patients with chronic pain shows that certain brainstem centres communicate, via descending spinal cord pathways, with small nerve cells in the superficial dorsal horn (SDH) of the spinal cord. These SDH neurones receive and process pain-signalling information from the skin ....Current treatments for chronic pain are limited in their success. This emphasises the need for new insights into the basic mechanisms and nervous system circuitry underlying altered or chronic pain states. Work in animals and patients with chronic pain shows that certain brainstem centres communicate, via descending spinal cord pathways, with small nerve cells in the superficial dorsal horn (SDH) of the spinal cord. These SDH neurones receive and process pain-signalling information from the skin and internal organs, and receive inputs from descending pathways. This descending input can either inhibit or enhance the activity of SDH neurones and subsequent pain perception. Till now it has been difficult to directly examine how descending pain pathways influence the small SDH neurones in the spinal cord. A new approach, which has been developed in our laboratory, now allows us to record from these very small SDH neurones in the spinal cord of an intact deeply anaesthetized mouse. In addition, our technique allows us to examine the recorded SDH neurone s responses to functionally relevant stimuli (brushing or pinching the hindpaw) as well as its physiology and anatomy. This project will use our new techniques to examine the effects of activating descending brainstem pathways that alter the way painful stimuli are processed in the spinal cord. The effects of altered levels of inhibition in the spinal cord will also be studied by using mice with naturally occurring mutations in their inhibitory glycine receptors. We believe a more complete understanding of pain processing mechanisms will be achieved by examining the role of descending pathways in an intact animal preparation. Such data are essential for the development of drug therapies that can successfully target pain syndromes.Read moreRead less