New research casts fresh light on the chronic pain mechanisms in irritable bowel syndrome (IBS), promising new and more effective treatments for the condition.
Between 25 and 45 million people in the United States are living with IBS, and up to 15% of the world’s population may have the condition.
The most common IBS symptoms include abdominal pain, bloating, and changes in bowel movements. Although other symptoms can accompany the illness, chronic pain is a key marker of the condition.
So what causes chronic pain in IBS? This is the question that researchers from Flinders University in Adelaide, Australia, set out to investigate in the hope that a better understanding of pain will lead to better treatments.
Professor Stuart Brierley, who is also a Matthew Flinders Research Fellow in Gastrointestinal Neuroscience, is the senior author of the new study, which appears in the journal JCI Insight.
Prof. Brierley and colleagues set out to investigate how the nerves in the gut trigger chronic pain in IBS, and whether it is the “irritated” nerves themselves that cause the irritability in IBS.
To do so, the team examined skin tissue because the skin is prone to both pain and itching. The authors explain in their paper that itching, like pain, has a protective role.
Itching causes scratching, which clears the skin of irritants, just like pain triggers withdrawal or avoidance of harmful stimuli.
“Patients with IBS [experience] chronic abdominal pain and experience rewiring of their nervous system so they feel pain when they shouldn’t — we decided to ask important questions about how nerves in the gut are activated to cause pain in order to seek out potential solutions,” says Prof. Brierley.
Preclinical experiments in mice showed that “receptors that mediate itch in the skin also mediate pain in the gut,” the researcher explains in the video below:
Prof. Brierley and his colleagues used agonists — or activating compounds — for these itch receptors and found that they also activated colonic sensory neurons both in vitro and in vivo in mouse models.
Furthermore, administering several of these agonists individually in the mice’s colons triggered a “pronounced visceral hypersensitivity to colorectal distension.”
Administering several of these agonists at once “as an ‘itch cocktail’ augmented hypersensitivity to colorectal distension and changed mouse behavior,” the researchers write.
“We found receptors that bring about an itchy feeling on [the] skin also do the same in the gut, so [IBS] patients are essentially [living with] a ‘gut itch,'” says Prof. Brierley.
“We’ve translated these results to human tissue tests and now hope to help create a treatment where people can take an oral medication for IBS.”
Prof. Stuart Brierley
The researcher explains that in IBS, chronic pain occurs when the itch signal pairs up with the so-called wasabi pain receptor, also known as the TRPA-1 ion channel. The Wasabi receptor is part of the family “Transient receptor potential (TRP) ion channels.”
“If you think about what happens when you eat wasabi,” says Prof. Brierley, “it activates a receptor on the nerves and sends a pain signal — that’s exactly what’s happening within [the] gut as [people with IBS] experience an itchy effect or wasabi effect in the gut.”
Directly targeting these receptors, explain the authors, may effectively treat chronic pain and discomfort in IBS.
“Having shown these mechanisms contribute to chronic gut pain, we can now work out ways to block these receptors and thereby stop the ‘gut itch’ signal traveling from the gut to the brain. This will be a far better solution than the problems currently presented by opioid treatments.”