Mechanosensitive afferent nerves and gastrointestinal motility

Funded Activity 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 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.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $384,693.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical bacteriology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

dorsal root ganglia | gastrointestinal motilty | irritable bowel syndrome | motility disorders | motility-related pain | pain | primary afferent neurones | vagus nerve

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