Mechanosensitive Afferent Nerves And Gastrointestinal Motility
Funder
National Health and Medical Research Council
Funding Amount
$384,693.00
Summary
This project aims to identify the different types of sensory nerves from the gut which cause sensations such as fullness, nausea or pain. These sensory nerves also activate important reflexes that coordinate different regions of the gut to ensure that food is properly digested and propelled. Many studies have examined these sensory nerves and how they can be activated by stretching the gut wall, but very basic questions remain to be answered. We do not know how many different types of sensory ne ....This project aims to identify the different types of sensory nerves from the gut which cause sensations such as fullness, nausea or pain. These sensory nerves also activate important reflexes that coordinate different regions of the gut to ensure that food is properly digested and propelled. Many studies have examined these sensory nerves and how they can be activated by stretching the gut wall, but very basic questions remain to be answered. We do not know how many different types of sensory nerves there are and whether they all respond to stretch in the same way. We cannot identify their specialised endings in the wall of the gut. While these sensory nerves definitely respond to stretch, they are also known to respond to contractions of the gut wall. Despite this, we do not understand how the normal movements of the gut wall activate them, nor why some movements can lead to pain. Most of the experiments will be carried out on small pieces of tissue taken from humanely killed guinea pigs and studied, under highly controlled conditions, in organ baths. The remainder of the study will be on specimens of human gut tissue obtained at surgery. This project will use new techniques to record sensory nerves during both stretch and contraction of the gut wall to understand what activates them. In addition, their endings will be labelled with dye to reveal their different shapes. Using computerised imaging techniques we will identify whether they respond to particular patterns of movement in the gut wall. Lastly we will record from these sensory neurones in live specimens of human colon to see whether the same types of sensory nerves are present in humans as in the small animals. This study will provide the first comprehensive account of sensory nerves to the gut wall that respond to distension, including those that activate pain pathways. This is a pre-requisite for designing new drugs that will target these nerve cells with minimal side effects.Read moreRead less
Gastrointestinal Sensory Function In Normal And Diseased States
Funder
National Health and Medical Research Council
Funding Amount
$691,026.00
Summary
Chronic pain and discomfort from the digestive system is a major health care issue world-wide. There is currently no effective treatment for these problems, which often have no apparent organic cause. Lack of treatment is due to a lack of understanding about how sensations are transmitted from the digestive system to the brain. Our research group has unique and powerful techniques that allow us to probe the basic mechanisms of sensory function, and make rapid progress towards finding drugs that ....Chronic pain and discomfort from the digestive system is a major health care issue world-wide. There is currently no effective treatment for these problems, which often have no apparent organic cause. Lack of treatment is due to a lack of understanding about how sensations are transmitted from the digestive system to the brain. Our research group has unique and powerful techniques that allow us to probe the basic mechanisms of sensory function, and make rapid progress towards finding drugs that reduce specific types of sensory signals from the gut. We shall investigate sensory mechanisms in the upper and lower regions of the gut, where symptoms are most prevalent in diseases such as non-cardiac chest pain, functional dyspepsia and irritable bowel syndrome. Six aspects of sensory nerve endings in the gut are to be investigated: 1. The grouping of endings into functional classes (similar to touch or pressure receptors in skin) 2. How endings respond to chemicals and hormones found in the gut 3. How currently available drugs may be useful in reducing sensitivity 4. The mechanisms by which inflammation affects sensitivity 5. How nerve growth factors may trigger changes in sensitivity 6. How pores or channels in nerve endings determine their functionRead moreRead less
The applicant aims to improve treatment of digestive disease by identifying and understanding the interactions between the nervous system and the gastrointestinal (GI) tract, with emphasis on sensory systems.
Morphological Determinants Of Neurotransmission In Autonomic Ganglia.
Funder
National Health and Medical Research Council
Funding Amount
$450,111.00
Summary
The nervous system consists of billions of nerve cells that are connected together in special ways to process information about the outside world and our internal state and then generate the appropriate responses of our body to this information. To understand the complex working of the brain and its nerves, we have to understand how all these nerves are connected to each other. We are interested in the nerves that control the functions of the internal organs, such as arteries, glands and the gut ....The nervous system consists of billions of nerve cells that are connected together in special ways to process information about the outside world and our internal state and then generate the appropriate responses of our body to this information. To understand the complex working of the brain and its nerves, we have to understand how all these nerves are connected to each other. We are interested in the nerves that control the functions of the internal organs, such as arteries, glands and the gut. The brain controls these functions automatically, so we usually are not directly aware of their activity. The instructions to change the activity of the internal organs are sent from the brain down the spinal cord. The information is then sent from the spinal cord to the organs via a special set of nerves. However, instead of going directly to their targets, these nerves make connections with yet another set of nerves, which then go on to make the final connections with the appropriate target organs. We know a lot about these final nerve cells, including how big they are, how complicated they look, and what kinds of chemicals they use to send messages to the organs that they control. However, we still do not very much about how all these nerves are connected to each other. In this project we will use different types of modern microscopes that use either lasers or electron beams to look directly at the nerves and their connections. We then will use computerised models to construct a detailed map of the pathways taken by the nerves on their way to their target organs. By knowing how the nerves are connected to each other in these pathways, we will be able to understand how the instructions of the brain are modified depending on what other things are going on in the body at the same time. This information will be vital to help us appreciate how the nerves work when we get sick or injured.Read moreRead less