Understanding and targeting centrally mediated visceral pain in inflammatory bowel disease

Chronic abdominal pain is a debilitating symptom of inflammatory bowel disease (IBD): a chronic inflammatory condition of the gastrointestinal tract, which includes Crohn’s disease (CD) and ulcerative colitis (UC), and is characterised by periods of inflammation and remission. During inflammation, pain is often present due to the activation of afferent nerve endings in the gut by inflammatory mediators (Beyak and Vanner, 2005). Importantly, pain associated with IBD often persists after inflammation has resolved, based on clinical and endoscopic examination, and is often “referred” from the gut to cutaneous or other visceral regions (Minderhoud et al., 2004). Based on what we know about pain processing circuits, this suggests the source of chronic and referred pain lies within the central nervous system (CNS). These clinical observations are supported by work in animal models of visceral inflammation that have provided behavioural, anatomical, molecular and physiological evidence to implicate spinal circuits in the development of altered pain responses in IBD (Farrell et al., 2014). In spite of this evidence, little is known about the precise mechanisms of chronic pain development and maintenance in IBD. This lack of understanding severely limits current therapeutic approaches for IBD pain management.