Many people with inflammatory bowel disease (IBD) experience pain. In fact, research shows
up to 70 percent of people experience symptoms of pain during a flare-up, and between 20 and 30 percent experience ongoing pain during periods of remission. Pain can severely affect quality of life and mental health, making it crucial for us to pinpoint the causes, understand how people with IBD experience pain, and discover ways to effectively manage it.
A team of researchers from Queen’s University and New York University College of Dentistry set out to do just that. Funded in part by Crohn’s and Colitis Canada, the researchers conducted a study using a preclinical mouse model of ulcerative colitis to identify how to effectively manage pain in IBD.
Ulcerative colitis is a form of IBD marked by inflammation of the large intestine that causes gut tissue to become acidic. The researchers took advantage of the acidic nature of the inflamed gut in mice with ulcerative colitis to test an opioid drug that works optimally when it is in an acidic environment. The goal? To identify a pain reliever that has minimal effect on normal tissues, thus minimizing the risks associated with opioid use.
Published in the prestigious journal GUT, the study’s findings point towards a promising new treatment for pain. The researchers found that a targeted novel opioid called
NFEPP can preferentially treat diseased tissue and spare healthy tissue, meaning that NFEPP can relieve pain without the devastating side effects.
Funding from Crohn’s and Colitis Canada awarded to Dr. Stephen Vanner of Queen’s University, through a three-year
Grants-in-Aid of Research Award, was instrumental in making this discovery possible.
“This novel pain treatment has the potential to dramatically improve our ability to help patients suffering from IBD-related pain, and its discovery would not have occurred without the funding from Crohn’s and Colitis Canada. “
How did researchers discover the powerful role of the NFEPP opioid?
Effective in treating pain in people with IBD, opioids bind to opioid receptors, including the mu opioid receptor. However, when opioids activate the mu opioid receptor in healthy tissue, it can cause severe and life-threatening side effects, including difficulty breathing, constipation, sedation, and addiction.
NFEPP is a reengineered form of the opioid fentanyl; an added fluorine atom helps the drug to only bind to the mu opioid receptor in an acidic environment. This steers the NFEPP to diseased tissues – sites of inflammation or injury – that become acidic due to localized changes in tissue metabolism.
The researchers investigated the use of NFEPP and fentanyl in mice with and without colitis. Both NFEPP and fentanyl inhibited colon pain in mice with colitis, however, unlike fentanyl, NFEPP did not cause side effects such as constipation, suppressed breathing, and altered movement. It also did not alter pain or cause side effects in mice without colitis.
This study shows NFEPP leaves healthy tissues untouched, as it targets opioid receptors in acidic tissues, thereby relieving pain in the inflamed colon. This could allow people with IBD to experience pain relief without the detrimental side effects often associated with other opioids.
What’s next?
The research team is working to test NFEPP’s ability to inhibit pain in the
human gut and ultimately conduct clinical trials. Potential treatments that target specific opioid receptors in diseased tissue could be a game-changing discovery, not only for pain management in IBD, but also for other diseases, such as cancer.
Read the full study
Agonist that activates the µ-opioid receptor in acidified microenvironments inhibits colitis pain without side effects to learn more.
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