Abdominal pain models: mechanisms and therapies and experimental models

Abstract

Chronic or recurrent abdominal pain is the most prevalent gastrointestinal disorder, affecting 10% of the general population, including children and adolescents. It is a common feature of both intestinal functional disorders, like irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBDs). These two conditions often overlap from the clinical point of view since a large subset of IBD patients experience persistent abdominal pain even after reaching remission from the intestinal inflammation, developing a condition called IBS-like. Visceral pain management is a major clinical problem in these patients since the lack of effective and safe drugs. Despite the large number of sufferers, the mechanisms that drive the development and the persistence of chronic abdominal pain remain largely unresolved and this presents a major barrier to progress in the development of new therapies. Chronic abdominal pain often displays a complex nature with mixed nociceptive, inflammatory, emotional and neuropathic components. This is mainly attributable to the intricated regulation of visceral sensitivity which involves many actors in the gut as well as in the peripheral and central nervous systems. In this text we describe the neuroanatomical bases of visceral pain signalling, the pathophysiological mechanisms involved in pain persistence and how current treatments work, including an overview of potential new targets. In the context of drug discovery, the potential advantages and disadvantages of different preclinical models of visceral pain were also discussed.