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
Peripheral Neuropathy And Pain: Role Of The Sphingosine Kinase-sphingosine 1-phosphate System
Funder
National Health and Medical Research Council
Funding Amount
$282,905.00
Summary
Understanding the neural mechanisms that generate pathological pain remains one of the essential goals for the development of effective treatments for pain, chronic pain with less side effects. Lipids are able to modulate pain perception. We will determine the role of a molecule named sphingosine 1-phosphate as a basis for the development of therapies for the treatment of neuropathic pain.
Identification Of The Pain Pathway From The Rectum And Its Mechanisms Of Activation
Funder
National Health and Medical Research Council
Funding Amount
$566,931.00
Summary
Abdominal pain is one of the most common reasons why patients seek medical attention. It is now known that irritable bowel syndrome (IBS) is one of the major causes of abdominal pain, but the reason why people experience pain from the gut is not known. This project will identify which sensory nerves in the gut wall signal pain to the spinal cord during conditions that mimic IBS and the precise mechanisms that activate these sensory neurons during IBS-like inflammation will be investigated.
Analysis Of Functional Role Of The BDNF Precursor In Sensory Neurons
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Neurotrophins, which are generated from their precursors, are essential for the survival and function of the nervous system. One of neurotrophins, brain derived neurotrophic factor (BDNF), is made in sensory neurons and transported towards nerve terminals. Mutation of a single amino acid in the precursor of BDNF disrupts this transport. This project will examine whether the precursor of BDNF has any function within sensory nerves. We will examine whether the precursor of BDNF gets into the nerve ....Neurotrophins, which are generated from their precursors, are essential for the survival and function of the nervous system. One of neurotrophins, brain derived neurotrophic factor (BDNF), is made in sensory neurons and transported towards nerve terminals. Mutation of a single amino acid in the precursor of BDNF disrupts this transport. This project will examine whether the precursor of BDNF has any function within sensory nerves. We will examine whether the precursor of BDNF gets into the nerve via its receptors and whether it plays any role in the development of pain and maintenance of neuropathic pain after nerve injury. Successful execution of the project will eludicate mechanisms of pain, especially neuropathic pain, and will provide important information to assist in the design of drugs for neurological diseases.Read moreRead less
Ion Channels Underlying Inflammatory And Post-inflammatory Visceral Mechanical Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$453,439.00
Summary
Inflammation causes tissue damage that triggers ion channels within sensory nerve fibres to produce greater signals in response to mechanical events, causing acute pain. In chronic pain, although the inflamed tissue has healed, sensory nerve fibres fail to "reset" back to normal. Often chronic pain is more severe than acute pain. This project will identify which ion channels are responsible for signalling acute and chronic visceral pain, explaining why sensory nerve fibres fail to reset.
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.
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.
Transient Receptor Potential Channels (TRPs) As Transducers And Targets In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$669,130.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we perceive, such as heat, cold, touch and pain. Some TRP channels are specialized to signal pain from visceral organs, which we must investigate if we are to find treatments for visceral pain, which are currently lacking.