Understanding the causes of abdominal pain in Crohn’s and Colitis 2020

What the researchers will look at?

Abdominal pain is common in people with Crohn’s or Colitis and greatly reduces quality of life - whether that’s making it harder to sleep well, causing absence at work or school, or just being in constant pain. It’s a symptom that has an impact regardless of being in remission or in a flare-up. Pain is a complex behavioural response. In people with Crohn’s or Colitis, pain is likely to be triggered by mediators released from the diseased bowel. These mediators activate the pain-sensing nerves in the gut, resulting in the feeling of pain. 

Dr Bulmer’s research team previously found that the activation of pain-sensing nerves is greatest in people with Crohn’s or Colitis who report the highest levels of abdominal pain. Their current work is focussed on identifying which mediators are most responsible for activating these pain-sensing nerves. This newly funded research project will help to identify those mediators. 

The nerve-activating mediators may be different to the mediators that cause inflammation in Crohn’s and Colitis - as pain can affect patients regardless of whether they are in remission or a flare-up. Therefore, medicines that block the mediators involved in inflammation may not be the best treatments for abdominal pain. 

Dr Bulmer’s team recently found that one mediator, an enzyme called matrix metalloproteinase 12 (MMP-12), can activate pain-sensing nerves. It’s already known that MMP-12 is released from the bowel of people with Crohn’s and Colitis. As part of this project, the researchers will explore this new role for MMP-12 and other MMPs in activating nerves, to better understand what causes abdominal pain in people with Crohn’s or Colitis. 

What the researchers think this might mean for people with Crohn’s and Colitis? 

In exploring how different MMPs can cause abdominal pain, the researchers hope to find new targets for treatments to relieve abdominal pain. Medicines that block these mediators could be effective treatments of abdominal pain in people with Crohn’s and Colitis – and findings from this project could support the development of MMP inhibitors for the treatment of abdominal pain. 

The development of effective treatments for abdominal pain in people with Crohn’s and Colitis has the potential to significantly increase the quality of life for those that regularly experience this symptom.   

Who is leading this research: Dr David Bulmer, University of Cambridge 
Our funding: £69,978 
Duration: 3 years 
Official title of application: Matrix metalloproteinases, critical mediators of visceral nociception in inflammatory bowel disease