An Abnormal Inflammatory Response Following Wrist Fracture Causes The Development Of Complex Regional Pain Syndrome (CRPS).
Funder
National Health and Medical Research Council
Funding Amount
$99,073.00
Summary
This project will contribute essential knowledge about what causes some people to develop Complex Regional Pain Syndrome (CRPS). CRPS affects approximately 5% of people following a fracture but can also occur with minimal injury. Sufferers experience gradually worsening levels of pain, skin discolouration, poor quality of life, and often severe depression. We will investigate the most likely cause of CRPS, which is thought to be an abnormal inflammatory reaction following injury.
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
Molecular And Histopathological Investigation Of Stress Fracture Healing And Effects Of Anti-inflammatory Drugs.
Funder
National Health and Medical Research Council
Funding Amount
$412,652.00
Summary
Stress fractures are debilitating injuries affecting children, adolescents and adults in sport, and army recruits. They also occur in horse and greyhound racing, often resulting in euthanasia of the animals involved. They incur considerable costs in medical expenses, time lost from sport and interruption to military training. But, there is almost no information on the mechanism of healing of these fractures. Non-steroidal anti-inflammatory drugs (NSAIDs) are still the most widely used medication ....Stress fractures are debilitating injuries affecting children, adolescents and adults in sport, and army recruits. They also occur in horse and greyhound racing, often resulting in euthanasia of the animals involved. They incur considerable costs in medical expenses, time lost from sport and interruption to military training. But, there is almost no information on the mechanism of healing of these fractures. Non-steroidal anti-inflammatory drugs (NSAIDs) are still the most widely used medication in management of musculoskeletal injuries, yet their effect on healing of stress fractures is unknown. NSAIDs delay fracture healing, but until recently there has been no standardised way of studying stress fractures. We have created, for the first time, a well-characterised, non-invasive model of stress fractures in the forearm of rats that closely resembles the clinical situation. This provides a novel and unique opportunity to determine the histological and molecular mechanism of stress fracture healing, and to investigate effects of antiinflammatory-analgesic medications on this process. Rats will have an experimental stress fracture produced in one forelimb, and its healing will be examined up to ten weeks using microscopic investigation and analysis of the genes that are turned off or on to initiate the process. Groups of rats will also be treated with antiinflammatory drugs such as ibuprofen, specific COX-2 inhibitors and a new class of drugs that target early immune responses called C5a receptor antagonists. The analgesic Paracetamol will also be investigated as an alternative to the NSAIDs described above. There is widespread use of anti-inflammatory agents in managing stress fractures, so it is vital that their effects on stress fracture healing be examined. This project has enormous significance for optimising approaches for clinical management of stress fractures and for understanding the interaction of anti-inflammatory or analgesic agents in that process.Read moreRead less
Understanding The Association Between Low Back Pain And Risk Factors For Chronic Disease
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Being overweight or obese and smoking are believed to be significant contributors to the development of long term back pain. However we know little about the relationship between low back pain and these risks for chronic disease. This research aims to understand these relationships by testing if weight and smoking programs reduce low back pain disability in overweight or smoking patients, and secondly if back pain also influences risk factors for chronic disease.
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.
Randomised Trial Of Ibuprofen For The Prevention Of Ectopic Bone-related Pain And Disability After Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$364,217.00
Summary
Joint replacement is a well-established treatment for severe osteoarthritis of the hip. While most patients benefit substantially from the procedure, many still experience some pain and disability after surgery. New evidence suggests that one important cause of this pain and disability may be abnormal bone deposits that form in the muscles around the hip (ectopic bone formation) during the first few months after surgery. Ectopic bone formation is seen in about 40% of all patients with hip replac ....Joint replacement is a well-established treatment for severe osteoarthritis of the hip. While most patients benefit substantially from the procedure, many still experience some pain and disability after surgery. New evidence suggests that one important cause of this pain and disability may be abnormal bone deposits that form in the muscles around the hip (ectopic bone formation) during the first few months after surgery. Ectopic bone formation is seen in about 40% of all patients with hip replacements. If the formation is extensive, all movement of the hip is lost and revision surgery is necessary. However, even when the formation is less severe, movement at the hip can be restricted resulting in pain and disability. There is growing evidence that treatment with a non-steroidal anti-inflammatory drug at the time of surgery may halve the risk of ectopic bone formation. While this would be expected to decrease the risk and severity of post-operative pain and disability, there is little evidence available about the long-term effects of these drugs after hip replacement. For this reason, together with concerns about possible side-effect of these drugs, orthopaedic surgeons have generally been reluctant to prescribe these drugs routinely for the prevention of ectopic bone formation. Ibuprofen appears to be the non-steroidal anti-inflammatory drug with the lowest risk of side effects. If it was shown to be effective in reducing the incidence of pain and disability associated with ectopic bone formation after hip replacement, it may well be considered worthwhile by doctors and patients alike. If such benefits were realised, this preventive strategy is likely to be a highly cost-effective way to improve long-term outcome among the rapidly growing numbers of patients that receive hip replacements. This study will provide reliable evidence about the short and long-term effects of ibuprofen among 1,000 patients receiving hip replacements in Australia.Read moreRead less
The Role Of Suppressor Of Cytokine Signalling-3 (SOCS-3) In Chondrocytes During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$348,392.00
Summary
Cytokines are messenger proteins produced and secreted from one cell which then bind to specific receptors on the surface of other cells. After binding, a series of intracellular events occurs, termed signalling, that results in the target cell changing its behaviour. Cytokine signalling, if allowed to proceed unchecked, can result in various disease states. The suppressor of cytokine signalling (SOCS) proteins are key negative regulators of cytokine signalling within the cell. They are induced ....Cytokines are messenger proteins produced and secreted from one cell which then bind to specific receptors on the surface of other cells. After binding, a series of intracellular events occurs, termed signalling, that results in the target cell changing its behaviour. Cytokine signalling, if allowed to proceed unchecked, can result in various disease states. The suppressor of cytokine signalling (SOCS) proteins are key negative regulators of cytokine signalling within the cell. They are induced by a wide range of stimuli, especially from a group called the IL-6 family. We have preliminary data showing that cartilage cells (chondrocytes) normally produce a particular SOCS protein, called SOCS-3. We have also shown that when SOCS-3 production is dysregulated, the chondrocytes undergo excessive proliferation. Normal chondrocyte function is important during skeletal development and diseases such as osteoarthritis are thought to result from abnormal chondrocyte behaviour. It is likely that SOCS-3 has a key role in regulating chondrocyte function. The aim of this proposal is therefore to examine the role of SOCS-3 in chondrocytes, during development and in disease. Much of our understanding of the role of the SOCS proteins comes from the construction of mutant mice that lack a particular SOCS protein. When mutant mice are made that lack SOCS-3 in the whole animal the mice die before birth and so virtually nothing is known about the role of SOCS-3 in chondrocytes and the implications for cartilage in disease states, such as arthritis. To answer this we will create mice that lack SOCS-3 specifically in their chondrocytes. Evaluating the role of SOCS-3 in cartilage development and chondrocyte function during degenerative and inflammatory disease states is potentially of major clinical importance in improving our understanding of arthritis and of cartilage repair.Read moreRead less
Interrelationships Between The Disc And Bone Of Lumbar Spinal Segments
Funder
National Health and Medical Research Council
Funding Amount
$423,625.00
Summary
The cause of back pain due to osteoarthritis, osteoporotic vertebral crush fracture, and ageing is poorly understood. Vertebral deformity, intervertebral disc disorganisation, and change to vertebral bone structure are features associated with degeneration of the spine and with back pain. Degenerative disc disease is one of the major causes of back symptoms and is believed to be associated with degeneration of the spine. Spinal degeneration includes disc degeneration, facet joint osteoarthritis, ....The cause of back pain due to osteoarthritis, osteoporotic vertebral crush fracture, and ageing is poorly understood. Vertebral deformity, intervertebral disc disorganisation, and change to vertebral bone structure are features associated with degeneration of the spine and with back pain. Degenerative disc disease is one of the major causes of back symptoms and is believed to be associated with degeneration of the spine. Spinal degeneration includes disc degeneration, facet joint osteoarthritis, compromised vertebral body bone quality, muscle and ligament alterations. It is assumed that these changes result in increased or abnormal spine motion and modified load distribution across the spinal joint. It has been found that with age, there is increased disorganisation of the intervertebral disc and decreased quality of vertebral cancellous bone. However, bones with the same density within the range of normal subjects, can show selective loss of bone structure and reduced load-bearing capacities of these vertebrae. An important concept here is that even for a given bone mass, fracture risk increases with age, supporting the view that there is a component of bone fragility that is independent of mass. Increased bone fragility may be associated with compromised cancellous bone structure. While the relationship between disc degeneration and changes in vertebral bone is commonly invoked, the mechanisms of this relationship have largely been overlooked, with age changes given more attention. However, it may be that intervertebral disc disorganisation modulates age-related bone changes within the spine. Disc degeneration may influence trabecular bone responses before changes with age put the patient at risk of vertebral crush fracture. We propose that the mature disc cannot effectively regenerate after damage, and thus responses to disc damage will be more readily observed in vertebral bone architecture than in the disc.Read moreRead less
Roles Of Injury-induced Inflammatory Response In Regulating Bony Repair At Injured Growth Plate Cartilage
Funder
National Health and Medical Research Council
Funding Amount
$366,301.00
Summary
Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play, trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth defects result from bony repair of the injured growth cartilage, w ....Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play, trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth defects result from bony repair of the injured growth cartilage, we largely don't understand why and how this bony repair occurs. Understanding mechanisms for this faulty bony repair of injured growth plate will be critical prior to effective biological treatments can be developed. Recently, using an injury model in young rats, we found that bony tissue formation at injured growth plate is preceded sequentially by inflammatory, fibrogenic, chondrogenic and osteogenic responses. The inflammatory response is an initial event and our recent studies suggest that inflammatory response recruits inflammatory cells and produces important molecules that could significantly influence subsequent fibrogenic, chondrogenic and osteogenic events leading to the bony repair of the injured growth plate cartilage. The current proposal further addresses roles of the inflammatory response and the molecular pathways of this response in regulating downstream bony repair events. This project will generate novel understanding on the faulty bony repair of injured growth plate, and will provide valuable information for developing cost-effective and simple therapeutic intervention that aims to prevent bony repair and to enhance cartilage regeneration of the injured growth plate in children.Read moreRead less