What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated with disease, for example, arthritis. Our laboratory has shown that a particular protein is a key mediator of inflammatory pain. The project is to understand how this particular protein promotes pain, including how it sensitzes neurons.
ENDOGENOUS PAIN RELIEF IN HEALTHY AND OSTEOARTHRITIC PATIENTS
Funder
National Health and Medical Research Council
Funding Amount
$509,926.00
Summary
Pain has a detrimental impact on ones quality of life and a significant financial impact on the community. Given this, there is a substantial effort aimed at developing pain relieving compounds. One way in which our own brain can provide complete pain relief is via a mechanism called diffuse noxious inhibitory control. We currently do not know how this mechanism works and the aim of this investigation is to explore this mechanism in healthy and osteoarthritis patients use human brain imaging.
Transcriptional Regulation Of Nociceptor Function And Extreme Genetic Pain Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,007,462.00
Summary
Disorders involving untreatable pain have a devastating impact on a patient’s quality of life. To better treat these conditions, we require a basic understanding of how sensory neurons work. In this study we will define the genetic network involved in regulating pain-sensing neurons. We will then search the genome of pain patients looking for coding mutations within this pain transcriptional network, and we will prove these mutations are causative in fly and mouse systems.
Importance Of CGRP Alpha In Pain Processing From The Large Intestine
Funder
National Health and Medical Research Council
Funding Amount
$548,289.00
Summary
This project will determine the mechanisms by which sensory nerve endings detect painful stimuli in the large intestine. The project will use a novel genetically modified mouse (that is only available in our laboratory) which allows us, for the first time, to visualize and record directly from the sensory nerve endings that detect painful stimuli and work out how this process occurs. We also identify a specific gene that is essential for detecting painful stimuli from this organ.
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
Synaptic Environment Of Nociceptive Inputs To The Spinal Cord
Funder
National Health and Medical Research Council
Funding Amount
$499,860.00
Summary
Pain affects everyone at some stage in their life. Usually, the pain subsides by itself as the underlying cause is resolved. Thus, the damaged tissue heals or we move away from a potentially injurious stimulus and we become free of pain. However, pain can persist for two main reasons: the underlying cause cannot be treated adequately and the painful stimulus continues; or the pain is maintained long after the primary stimulus has resolved. This ongoing pain often is resistant to alleviation by c ....Pain affects everyone at some stage in their life. Usually, the pain subsides by itself as the underlying cause is resolved. Thus, the damaged tissue heals or we move away from a potentially injurious stimulus and we become free of pain. However, pain can persist for two main reasons: the underlying cause cannot be treated adequately and the painful stimulus continues; or the pain is maintained long after the primary stimulus has resolved. This ongoing pain often is resistant to alleviation by common analgesics. Therefore, a major aim of the pharmaceutical industry is the development of new drugs to target persistent pain. This requires a thorough understanding of how the nerves that detect painful stimuli transmit that information into the spinal cord, and then on to the brain, where we construct a conscious perception of the pain. Various kinds of painful stimuli, such as tissue damage, noxious chemicals, or extreme temperatures, are detected by different types of nerves. Each nerve type can be identified by its characteristic chemical profile. Recently, we found that some of these nerves probably do not transmit their messages to the spinal cord in the way everyone had thought. This means that there must be an alternative way for many types of painful stimuli to be transmitted into the spinal cord. In this project, we will use a sophisticated suite of modern microscopic and electrical recording techniques to find out what this alternative mechanism is. Our central idea is that most types of painful stimuli simultaneously activate two types of sensory nerves. These nerves then connect with specific nerve cells in the spinal cord before painful information is relayed to the brain. Our proposal suggests a new mechanism for understanding how pain can develop from being an acute defensive reaction to a chronic problem. In turn, this should lead to improved strategies for developing and testing new analgesic drugs.Read moreRead less
Mechanisms Of Activation Of Vascular Afferent Nociceptors To The Gut
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
We have recently identified the nerve fibres responsible for detecting pain from the gut. In this project we will study exactly how these nerve cells are activated by movements of the gut wall, by changes in blood vessel diameter and how this can be studied most efficiently We will use this information to develop simple preparations in which to study these sensory nerves in animal and adult tissue to test which drugs may affect their excitability and hence be useful in treating gut pain.