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The anatomical, physiological, and molecular basis of chronic visceral pain in humans (Human visceral pain)
Date du début: 10 mai 2012, Date de fin: 9 mai 2014 PROJET  TERMINÉ 

Chronic visceral pain (CVP) is one of the most frequent reasons for seeking health care. Pain can arise from inflammatory disease, but 50% of patients with visceral pain have no diagnostic abnormalities, and are classed as “functional”. Both types of CVP are poorly understood, but animal studies show that they involve hypersensitivity of visceral sensory nerves, and some of the molecular mechanisms of hypersensitivity are emerging. We now need a translational program which identifies molecular targets and how they change in human disease. My work has investigated structure and function of visceral sensory nerves and identified mechanisms of hypersensitivity in animal models. Now I shall test these concepts in human tissue, and thus strengthen the basic-clinical interface in the biology of visceral pain.Major questions to be addressed are:1. What functional and anatomical subtypes of sensory nerves innervate the human colon?2. Which molecular targets exist in human sensory nerves that can be modulated pharmacologically?3. How is the structure, function and pharmacology of human sensory nerves altered in disease?I shall optimise methods for working with human tissue. This involves recording of sensory nerves in vitro from surgical resections of uninflamed, inflamed or hypersensitive human colon. This will show the different subtypes and modalities of sensory nerves in the human bowel, and their specialization for specific functions in pain vs other processes. It will also test the concept I generated from animal work, that certain channels and receptors are enriched in pain sensing nerves. This work will provide insight into how pain develops in human disease. Along with functional recordings, the expression of candidate molecules on sensory endings and their structure will be studied, to provide a complete picture in health and disease.An insight into ways to combat CVP will emerge from these studies. It also has ramifications for other pain pathologies.