Interaction Of TRP Channels And Inflammatory Mediators: A Critical Role In Visceral Pain
Funder
National Health and Medical Research Council
Funding Amount
$308,747.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we feel, such as touch and pain. The function of these channels can be altered by substances released by the body during inflammation. Some TRP channels have specialized roles in signalling pain from the colon which can be enhanced during colonic inflammation. Understanding how TRP channels and inflammatory mediators function and interact is essential if we are to find treatments for colonic pain.
Silencing Visceral Nociceptors By Targeting NaV1.1: A Novel Therapeutic Approach For Treating Irritable Bowel Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$696,809.00
Summary
Patients with Irritable Bowel Syndrome suffer from chronic abdominal pain and co-morbidities such as over-active bladder. These symptoms arise from sensory nerve fibres in the colon and bladder that signal pain to innocuous stimuli. We are excited to report that a specific voltage-gated sodium channel, called NaV1.1, plays a key pathological role in generating these symptoms. Here, we will specifically target and block NaV1.1 expressing pain-sensing neurons, provide key advances for therapies.
Is Overactive Bladder A 'Bladder Itch'? Identification Of Itch Specific Pathways Within The Bladder
Funder
National Health and Medical Research Council
Funding Amount
$720,585.00
Summary
Overactive bladder is a leading cause of nocturia, urgency and incontinence. These symptoms arise from sensory nerve fibres in the bladder. We have identified key irritant mechanisms, including the bile acid receptor TGR5 and Mrgpr family, thought to only exist in the skin, also innervate the bladder. We hypothesis that the clinical entity overactive bladder, is triggered by pathological activation of bladder afferents by such irritants and that overactive bladder is essentially a bladder itch.
A Novel Technique For Prolonged Silencing Of Visceral Pain Without Opiates
Funder
National Health and Medical Research Council
Funding Amount
$637,383.00
Summary
There has been substantial interest in the community for pain relief without opiates. This project demonstrates a new strategy to suppress pain at the source for prolonged periods, by suppressing activity in the sensory nerve endings that detect pain, not by acting in central pathways like opiates. To do this, we use a harmless virus to shut down a vital sodium channel for pain perception. These experiments use techniques that were recently developed in our lab and cant be performed elsewhere.
Life-threatening Ulcer Complications In The Elderly: Role Of Visceral Sensory Function And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
A large proportion of patients with chronic disease such as peptic ulcer disease present with life-threatening complications such as severe peptic ulcer bleedings without any relevant symptoms prior to the manifestation of the complication. This lack of symptoms can be considered the main reason that the disease is not earlier diagnosed or before severe complications such as life-threatening bleeding ulcers occur.
Can Persistent Bladder Pain Be Treated By Targeting TRPA1 Expressing Nociceptors?
Funder
National Health and Medical Research Council
Funding Amount
$687,730.00
Summary
Persistent visceral pain is extremely difficult to treat and manage. To solve this problem we need to understand how pain nerves in internal organs differ from those in skin and muscle. We have discovered a pain-detecting molecule TRPA1 in bladder sensory nerves. We aim to show how bladder inflammation changes the function of these bladder pain detectors and test a new way of selectively anesthetising them. We also will use a new technique to study how the bladder lining detects pain.
Is Abdominal Discomfort A “colonic Itch”? Identification Of Itch Specific Pathways In The Gut In Health And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$906,996.00
Summary
Chronic abdominal pain is a major worldwide problem. TGR5 and Mrgpr receptors are expressed by neuronal pathways innervating the skin, where they detect irritants and transmit itch. Our novel, innovative project shows a similar pathway exists within the viscera, which plays a major and unappreciated role in chronic abdominal pain. These receptors represent novel targets for therapeutic treatment, potentially creating multibillion-dollar savings to the Australian economy and healthcare systems.
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.
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.