The pain of Crohn's is so intense that only constant doses of morphine will help it subside, and even then the relief is heartbreakingly brief. It is so crippling that it can cause you to lose consciousness and vomit; like someone is cutting you open from the inside. Barry Edmondson
Crohn's patient
This project aims to identify how the sensation of pain is registered for people with Crohn’s disease. This is being done by using biopsies taken from patients having endoscopies.
How is the study of pain in Crohn’s disease being done?
The team are collecting biopsy samples from Crohn’s disease patients undergoing endoscopy at The Royal London Hospital. Patients were put into categories based on how active their disease was at endoscopy and by measuring serum C-reactive protein and faecal calprotectin levels.
- C-reactive protein is a substance produced by the liver in response to inflammation and is an indication of how active the disease is.
- Faecal calprotectin is released during periods of inflammation.
This test helps to distinguish between Crohn’s disease and Ulcerative Colitis.
Additionally patients were put into categories according to the intensity and frequency of their abdominal pain.
The substances found in examining the biopsies was matched against the patient’s reporting of pain to determine which substances were most likely to be linked to pain sensations.
The research team
The Principal Investigator is Dr David Bulmer, Lecturer in Neurogastroenterology at the Wingate Institute. He is assisted by a post-doctoral researcher using the facilities of the National Bowel Research Centre.
Why study pain in Crohn’s disease?
Abdominal pain is a big feature of living with Crohn’s and is identified as a key issue to tackle by Crohn’s patients. Often patients have to be hospitalised to bring it under control so that morphine can be used. Morphine use itself brings problems, including slowing down the bowel which can bring a new range of problems.
Final Report Summary
The aim of this project is to develop the use of human tissue samples taken from patients with Crohn’s disease to study the causes of abdominal pain in Crohn’s disease. To do this, we have incubated these samples in a physiological solution to generate a “human disease” supernatant or solution, which contains the mediators released from the inflamed tissue. We believe these mediators cause pain in Crohn’s disease by activating the pain-sensing nerves within the gut. By identifying new approaches to prevent the activation of nerves by these mediators, we can help develop novel treatments for abdominal pain in Crohn’s disease.
We have examined the effects of Crohn’s disease supernatants on nerve activity and identified a protein (NaV1.9) present on nerves which is essential for their activation by these disease supernatants. We have published this work in PAIN, the official journal of the International Association for the Study of Pain, and NaV1.9 is now considered an important approach to the treatment of pain in Crohn’s disease.
Finally we have also examined the composition of supernatants taken from patients with Crohn’s disease, Ulcerative Colitis and functional abdominal pain and compared the effects of the supernatant on nerve activity with mediator levels and pain scores reported by the patient. Changes in nerve activity correlated with levels of IL-8 a marker of mucosal inflammation, in the supernatant. IL-8 levels, in turn, were found to correlate with pain scores. A manuscript is now being prepared on this work for submission to Journal of Crohn’s and Colitis.