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
We use a mouse model of inflammatory bowel disease (IBD) to determine how sensations from the inflamed gut are processed in the spinal cord. Over 60,000 Australians suffer from IBD and debilitating pain is a major symptom. Surprisingly, we know very little about how pain signals originating in the normal or the diseased gut are organised and processed in the central nervous system. Obtaining such information is a necessary first step before we can develop therapies to relieve gut pain.
Spinal Cord Injury Pain: Understanding Mechanisms To Develop Treatments
Funder
National Health and Medical Research Council
Funding Amount
$597,675.00
Summary
Spinal cord injury has devastating effects on health and quality of life. Many of the major consequences of injury, such as chronic pain and loss of voluntary voiding, are "invisible" – i.e., they are not as visible as limitations of mobility. Our study aims to define the neurobiological changes that cause development of persistent pain after spinal cord injury and use pharmacological tools to attenuate the development of pain.
Development Of Peripheral Sensory Pathways In Humans
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
To receive the appropriate information about the state of our muscles, joints, organs, and skin we need a properly 'connected' sensory system. Recent evidence suggests traumatic events during early development can alter sensory connections within the spinal cord. This can lead to debilitating movement disorders, digestive diseases, and increased pain. In this study we will examine how peripheral sensory fibres connect with the appropriate nerve cells in the human spinal cord during development.
Although chronic pain is a serious clinical problem, treatments for its alleviation have largely failed, in part because they have not been tailored to the specific origin of the pain. This proposal focuses on rheumatoid arthritis, a common and incurrable source of chronic pain. This study will investigate how specific changes in spinal cord nerve cells contribute to chronic arthritic pain. The outcomes will help identify new targets to treat chronic pain in rheumatoid arthritis.
Training-induced Restoration Of Topographic Maps And Vision During Opticnerve Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$379,725.00
Summary
The mature brain and spinal cord, or central nervous system (CNS), are extremely complex. A consequence of such complexity is that little if any spontaneous repair or regeneration occurs after damage. Brain injury and para- or quadriplegia thus inflict extremely high costs on the individual and to society, estimated at approximately $1 billion annually in Australia. One of the greatest medical challenges therefore is to restore function following neurotrauma. One of the most exciting advances, h ....The mature brain and spinal cord, or central nervous system (CNS), are extremely complex. A consequence of such complexity is that little if any spontaneous repair or regeneration occurs after damage. Brain injury and para- or quadriplegia thus inflict extremely high costs on the individual and to society, estimated at approximately $1 billion annually in Australia. One of the greatest medical challenges therefore is to restore function following neurotrauma. One of the most exciting advances, however, over the last decade is the recognition that the adult CNS, particularly after damage, does have a capacity for repair and that appropriate neural activity, produced either via relevant experience or specific training, is essential in driving the repair process to produce useful behavioural recovery. One of the clearest examples comes from our laboratory in which we have recently shown that training animals on specific visual tasks during optic nerve regeneration allows useful vision to be restored; untrained animals are blind via the experimental eye. The advantage of the visual system is that it is a relatively simple part of the CNS with one major class of nerve cell projecting to well defined and accessible brain regions. The significance of the project is that, for the first time, we are able pinpoint specific training-induced effects within identified nerve cells and their connections, a task that is much harder within other CNS regions. In particular, we will examine molecular, anatomical and functional changes that are induced via training and explore whether intervention with blockers of inhibitory neurotransmission further improves the beneficial effects of training. Understanding the changes in nerve cells that underlie the positive effects of training after neurotrauma will have implications for the continuing development of rehabilitation strategies for improved recovery after CNS injury.Read moreRead less