Mechanistic stratification of visceral pain using human tissue
The perception of visceral pain is a complex sensation evoked by a diverse range of gastrointestinal diseases. Despite heterogeneity in pain pathophysiology, we frequently seek to develop mono-therapeutic analgesic approaches with mixed success. Here we describe a series of studies, which have used human tissue to study peripheral sensitisation across a range of gastrointestinal diseases from appendicitis to irritable bowel syndrome (IBS). These studies have provided (1) a mechanistic basis for the loss of pain sensation with age, (2) the identification of novel proteinase and lipid mediators of visceral nociception, and (3) the opportunity to stratify patients based on disease specific mechanisms of peripheral sensitisation, promoting personalised medicine approaches to the treatment of visceral pain, a leading cause of lifelong morbidity in gastrointestinal disease.