Why Do People Keep Hurting Their Back: A Longitudinal Study Of Biological, Psychological And Social Predictors
Funder
National Health and Medical Research Council
Funding Amount
$739,946.00
Summary
We aim to identify why people continue to suffer episodes of back pain. If we can identify factors that predict the course of back pain we can target treatments to the right people to reduce the burden of this common condition. We will follow people for a year after an acute episode. We will measure novel issues like control of trunk muscles, inflammatory response, and how the nervous system deals with pain. We will also investigate how these factors interact with social and psychological issues
Mechanisms Of Serotonergic And Triptan Mediated Analgesia Within The Midbrain
Funder
National Health and Medical Research Council
Funding Amount
$546,937.00
Summary
Chronic pain requires multiple pharmacological interventions and these are often ineffective. These drugs include those which act on a diverse group of cell-surface proteins, called serotonin receptors. This project will use cellular and whole animal techniques to examine how these agents act within intrinsic pain and anxiety control systems within the brain in order to identify novel analgesic pharmacotherapies with enhanced efficacy and reduced side effects.
THE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES TO DEEP AND SUPERFICIAL PAIN IN HUMAN SUBJECTS
Funder
National Health and Medical Research Council
Funding Amount
$375,750.00
Summary
Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes ....Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes changes in blood pressure, heart rate and motor activity (often in an attempt to remove the source of the pain). The proposed research aims to characterise the cardiovascular and motor patterns associated with pain originating in skin and in muscle and to examine the brain regions that produce these changes. More specifically, microelectrodes will be used to investigate changes in peripheral nerve activity during transient painful skin and muscle events in awake human subjects. In a separate investigation functional magnetic resonance imaging will be used to determine brain sites that are activated by skin or muscle 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
Contributions Of Intrinsic Renal Cells To Inflammatory Renal Injury
Funder
National Health and Medical Research Council
Funding Amount
$66,433.00
Summary
These studies aim to improve our understanding of glomeruonephritis, the most common cause of kidney failure. They will study the interactions between circulating white blood cells (leukocytes) which originate from the bone marrow , and intrinsic kidney cells in the development of tis disease. Inflammation is the result of recruitment of bone marrow derived inflammatory cells and plasma proteins to a variety of stimuli. The subsequent injury represents the interaction between recruited cells and ....These studies aim to improve our understanding of glomeruonephritis, the most common cause of kidney failure. They will study the interactions between circulating white blood cells (leukocytes) which originate from the bone marrow , and intrinsic kidney cells in the development of tis disease. Inflammation is the result of recruitment of bone marrow derived inflammatory cells and plasma proteins to a variety of stimuli. The subsequent injury represents the interaction between recruited cells and local cells within the target organ. Glomerulonephritis is an important human disease where both bone marrow derived inflammatory and local cells have the potential to contribute to kidney injury by production of signalling molecules called cytokines. This study will determine the contribution of specific cytokines produced by intrinsic renal cells towards the development of inflammatory kidney injury in GN.Read moreRead less
Speech and chewing are accomplished automatically by the jaw muscles which have both the power to chew meat and even bone, and the precision to make extremely fine adjustments to the shape of the mouth that enable speech. The brain needs constant inputs from sensory receptors in and around the mouth to control these muscles. We will investigate how these sensory mechanisms automatically fine-tune the activity of the jaw muscles and the mechanisms that keep the jaw in its normal position when the ....Speech and chewing are accomplished automatically by the jaw muscles which have both the power to chew meat and even bone, and the precision to make extremely fine adjustments to the shape of the mouth that enable speech. The brain needs constant inputs from sensory receptors in and around the mouth to control these muscles. We will investigate how these sensory mechanisms automatically fine-tune the activity of the jaw muscles and the mechanisms that keep the jaw in its normal position when the subject is sitting quietly, or when the head is moving up and down during running. This normal rest position of the jaw is a vital point of reference for dentists who are making false teeth and for surgeons who are restoring damaged faces, but it is not known what mechanisms are responsible for it. Anyone who has experienced a sore tooth or sore jaw muscles will know that pain adversely affects normal chewing. A common symptom is limitation of jaw movements. We will determine how pain affects the control of jaw muscles. This is important for people with chronic facial pain from arthritis of the jaw joint or from grinding their teeth while they are asleep. Even if it is not possible to eliminate their pain, we hope to suggest approaches which will alleviate its effects. Another part of our study involves a computer model of the chewing system. Computer models enable scientists to examine the effect of various interventions such as surgery or orthodontics on a model before these are tried on humans. It is also possible to use such a virtual patient to answer important functional questions that cannot be examined in humans because the methods are unavailable, or because the procedures would be ethically unacceptable. The current version of the computer model is quite sophisticated anatomically, but lacks important information on the control systems that activate the muscles. We will collaborate with the developers of the model by providing this information.Read moreRead less
Pain And Trunk Muscle Control: Effects, Mechanisms And Consequences
Funder
National Health and Medical Research Council
Funding Amount
$296,452.00
Summary
Twenty-one percent of Australians report long-term back problems. This makes back pain the most common chronic pain in Australia and most prevalent disorder among the National Health Priority Areas. For the majority with recurrent and chronic problems, the cause is unknown but changes in control of the spine are thought to be important. It is well accepted that pain and injury to the low back affect the way that we control the back muscles and this leads to changes in spinal function. However, d ....Twenty-one percent of Australians report long-term back problems. This makes back pain the most common chronic pain in Australia and most prevalent disorder among the National Health Priority Areas. For the majority with recurrent and chronic problems, the cause is unknown but changes in control of the spine are thought to be important. It is well accepted that pain and injury to the low back affect the way that we control the back muscles and this leads to changes in spinal function. However, despite considerable investigation of this problem, there is a distinct lack of consensus for how the control of movement is changed during pain, why it changes, and whether these changes lead to further problems in the long term. The objective of this series of studies is to determine how the adaptation to pain changes the control of the spine. We will use a range of techniques that include tests of the strategies used by the brain to control the spine and mathematical models to estimate the effect that these changes have on the spine when people are given back pain by injecting sterile salty water into the back muscles. These studies will be backed up by measures of mechanical properties of the spine and by comparison to people with clinical pain. This combination of methods has not been used previously and is likely to help resolve the problem of how muscle control is chaged in back pain. We will also test a range of hypotheses regarding how pain has its effect on muscle activity. A final series of studies aims to determine whether the failure of these changes in muscle control to resolve after an epiosde of back pain leads to increased recurrence of pain in the long-term. The importance of this project is highlighted by the significance of back pain as a major health issue, the lack of consensus regarding the effect and mechanisms of pain on trunk muscle control (despite extensive investigation), and the potential for the findings to guide rehabilitation and management.Read moreRead less
Pain changes movement. Although undisputed, there is a surprising lack of agreement regarding the underlying mechanisms. This project involves an innovative mix of neurophysiological methods to investigate the drive to muscle cells from the nervous system and changes in the mechanics of contraction. These studies will resolve the perplexing problem of how pain changes our ability to activate muscle. Clear understanding of the underlying mechanisms can guide rehabilitation.
Stimulus Induced Synaptic Plasticity In The Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$428,777.00
Summary
Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating ....Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating doses required for adequate pain relief and the limited efficacy of current drug therapies in some clinically important pains states. The persistence of pain after the original injury has resolved suggest the development of adaptations that result in the ongoing pain. The changes in neurobiology underlying persistent pain are poorly defined. A better understanding of this neurobiology will result in better therapeutic approaches to persistent pain. The amygdala is a brain region that is important for pain processing, endogenous analgesia and emotion. A neuronal pathway that delivers information about pain to the amygdala has recently been shown to be critical for the development of persistent pain. Little is known about whether this critical neuronal pathway is modified by pain. This project will determine using electrical and chemical techniques how a brief or persistent painful stimulus changes the delivery of painful information to the neurons in the amygdala. The changes produced by a brief painful stimulus likely represent the initial changes in the development of a persistent pain state. This information may allow us to more fully understand the transition from acute to persistent pain and the changes defined may be sensitive to pharmacological modulation. Preventing or inhibiting these pain induced changes may provide better treatment for persistent pain or ideally prevent people undergoing the transition from acute to persistent pain.Read moreRead less
Physical, Lifestyle And Psychosocial Determinants Of Spinal Pain Development In Adolescents
Funder
National Health and Medical Research Council
Funding Amount
$682,800.00
Summary
This project aims to understand the development of back and neck pain in adolescence. By the age of 16 around half of all adolescents have suffered back pain and one third have suffered neck pain. For many adolescents this pain is disabling and over a third of sufferers miss school, miss recreation and seek medical help. The current understanding of back and neck pain in adolescence is quite limited - restricting the effectiveness of initiatives to prevent adolescents having to suffer spinal pai ....This project aims to understand the development of back and neck pain in adolescence. By the age of 16 around half of all adolescents have suffered back pain and one third have suffered neck pain. For many adolescents this pain is disabling and over a third of sufferers miss school, miss recreation and seek medical help. The current understanding of back and neck pain in adolescence is quite limited - restricting the effectiveness of initiatives to prevent adolescents having to suffer spinal pain and of treatment of those adolescents unlucky enough to have an episode. Better understanding and interventions for adolescent spinal pain will also have longer term implications by reducing adult spinal pain. Four out of 5 adults will experience spinal pain. In the USA treating adult back pain is the 4th largest health care cost. Many adults with chronic back pain had their first episode during adolescence. A better understanding of spinal pain in adolescence may help prevent it developing into a lifelong disability. We will collect information from 2,000 adolescents on their experience of back and neck pain and on potential physical, lifestyle and psychosocial risk factors. We believe factors such as their posture, muscle capacity, TV and computer use, mental health and social situation all combine to influence whether a person develops back or neck pain. The project is unique as it will not only collect a broad range of information during adolescence, but will also make use of a large database of health, developmental and psychosocial information already collected from these children since birth. With a better understanding of the development of spinal pain we will be able to develop guidelines to help prevent these problems. We will also be able to develop better treatment plans for sub-groups of adolescents with a particular combination of risk factors. Together these initiatives will assist in understanding and breaking the pathway to chronic spinal pain.Read moreRead less