Solving the IBD Chronic Pain Crisis

Up to half of all people with an inflammatory bowel disease cope with ongoing pain, even if they aren’t in the midst of a flare. But new research efforts are taking a multi-pronged approach in the search to find relief that works.

Medically reviewed by: Mona Rezapour, M.D.

This content was created as a collaboration between HealthCentral and the Crohn's & Colitis Foundation.

Even in moments when scans or lab work showed her Crohn’s disease to be under control, Dee Dee Branchaud’s abdominal pain has never truly quieted down. No matter what treatment she’s received, “pain is always present. It never goes to a zero,” says the 48-year-old from Providence, RI, who was diagnosed in 2022.

A busy pharmacist and mom, she’s tried her best to adapt, balancing work, surgeries, and daily life while managing a baseline of constant discomfort, punctuated by flares, abscesses, and joint pain that often appear without warning. “It’s always there, reminding you. I have to push through it for my son or a friend. I do it, but I always know I’ll have to go back to bed as soon as I get home,” she says.
 

Branchaud is far from alone. “Chronic pain is one of the most persistent and devastating challenges facing people with inflammatory bowel disease (IBD),” says Andres Hurtado-Lorenzo, Ph.D., the senior vice president of translational research & IBD ventures at the Crohn’s & Colitis Foundation. (IBD is an umbrella term for chronic inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, or UC.) And while pain is often assumed to be a symptom of active disease, up to 50% of IBD patients continue to have pain even after they’ve reached remission, according to research led by Hurtado-Lorenzo and published in the Foundation’s journal Crohn’s & Colitis 360.
 

The drivers of this pain still aren’t fully understood. What’s more, we’re sorely lacking in effective therapies. “It’s a major unmet need,” acknowledges Alan Moss, M.D., the chief scientific officer at the Crohn’s & Colitis Foundation. There are currently no FDA-approved therapies for IBD focusing on pain. Moreover, the most commonly used pain relief options aren’t ideal for long-term use: Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen can pose serious GI risks for people with IBD, while opioid pain relievers are often addictive and can lead to GI issues like constipation, per the Foundation.

Clearly, we need to do better. That’s why the Foundation has made chronic pain in IBD a research priority, creating the Chronic Abdominal Pain in IBD Research Initiative in 2022. The initiative continues to fund multiple landmark studies and convenes experts from around the world to find safer, more effective solutions to pain related to IBD. Here’s what they’ve learned so far—and where some potential solutions to IBD pain may be found.
 

Most people whose IBD isn’t well-controlled experience abdominal pain and cramping alongside other GI symptoms like diarrhea, urgency, or rectal bleeding. But the assumption is that the pain will go away once they find a treatment that gets them to remission. Except, that very often isn’t the case. “In [the Foundation’s] patient focus groups, a common theme was that even though their diarrhea and abdominal issues had improved, their pain issues had not,” says Dr. Moss.

To find out how common chronic abdominal pain in remission actually is, the Foundation conducted a population-level analysis using data from the 2023 National Health Interview Survey, which is a nationally representative public health survey. “Pain is considered chronic if it occurs consistently for three months or intermittently for six months,” says Orna Ehrlich, the Foundation’s chief of staff and impact.

Looking at data for more than 29,000 adults, the analysis—recently presented at Digestive Disease Week, with a related paper in the works—found that people living with IBD were nearly twice as likely to have chronic pain compared to those without the disease (47% versus 23%). They were also about 50% more likely to report their pain as severe. These patterns held true for people with Crohn’s and UC, regardless of factors like sex, race, income, insurance, or other health conditions.

Perhaps unsurprisingly, the data also quantified what people living with chronic pain already know all too well: It takes a major toll on your ability to live a normal life. Nearly a quarter of respondents with post-remission pain said that the pain frequently limited their activities, and around 13% said that it affected their family life. Previous studies, including a major systematic review published in 2025 in JAMA Network Open, have shown that chronic pain is also strongly linked to problems like depression and anxiety.
 

Pain during active Crohn’s or UC is well understood. When your GI tract is severely inflamed, it makes sense that you’d have some intense abdominal discomfort. But why do some people continue to experience chronic pain after their GI inflammation and other symptoms have cleared up?

The Foundation has convened leading experts in the fields of gastroenterology, neurology, and pain medicine, along with patients living with chronic pain and others to try to find the answers. Through the Chronic Abdominal Pain in IBD Research Initiative, they’ve learned that the problem is likely multifactorial. “Chronic pain in IBD is a complex biological and psychological process,” says Hurtado-Lorenzo.

The main driver is thought to be post-inflammatory visceral hypersensitivity, where inflammation from IBD causes the nerves in the gut as well as the brain to become overly reactive, even after the inflammation has cleared up. As a result, the nerves may end up misfiring in response to any kind of sensation, causing those sensations to be interpreted as pain, explain researchers in the Crohn’s & Colitis 360 article.

Hurtado-Lorenzo puts it like this: “Once you sensitize the nervous system [from previous inflammation], and the brain has been changed, it doesn’t matter if you no longer have inflammation.” In other words, the brain becomes primed for pain no matter what kind of signal it is receiving.

Still, this kind of post-remission hypersensitivity doesn’t happen to everyone with IBD. So why are some people affected while others aren’t? While the answer isn’t entirely understood, things like genetics, changes to the gut microbiome, metabolic compounds produced by bacteria in the gut, and even psychological factors like stress could play a role, according to the researchers. “It’s not equal in all patients,” Hurtado-Lorenzo observes. “We want to understand, what are the biological drivers that support or drive that particular clinical manifestation in each patient?”

Since chronic pain after remission likely has multiple culprits that may be different for different people, the solution isn’t one-size-fits-all. Instead, the goal “is to drive more personalized approaches for treatment, rather than treating chronic pain as a single, uniform symptom,” Hurtado-Lorenzo says.

To that end, the Chronic Abdominal Pain in IBD Research Initiative has awarded three major grants of over $900,000 each in the last three years aimed at better understanding—and combatting—chronic pain in IBD. “When we launched the initiative, we realized there were no papers on chronic pain in [IBD patients] and we’re talking about 30% to 50% of the patient population,” says Hurtado-Lorenzo. By supporting innovative research into why pain persists—and how it can be treated more effectively—the hope is to help pave the way toward the development of therapies that may eventually help a huge portion of people living with Crohn’s and UC.

Exploring the Brain, Gut, and Microbiome Connection

Can changing your microbiome help reduce pain from IBD? An ongoing British study that looks at this microscopic community of trillions of organisms in the gut is hoping to find out. “The bacteria living in the gut produce chemicals that influence the immune system, gut nerves, and the brain. In some people, this may keep pain pathways switched on even after the inflammation has settled,” explains Qasim Aziz, Ph.D. a professor of neurogastroenterology and the director of the Wingate Institute of Neurogastroenterology at the Queen Mary University of London in England.

To understand why pain goes away for some people with IBD once their inflammation dies down and sticks around for others, Aziz and his team are comparing what’s going on in the brain, intestines, and microbiome of some 300 IBD patients for several years post-flare by collecting detailed psychological and pain questionnaires, analyzing stool samples and colon biopsy tissues, and performing sensory testing on study subjects. The study is expected to be completed by the end of 2026.

While it’s too early to speculate on the findings, the hope is that the research team will uncover distinct biomarkers for patients who experience chronic pain versus those who don’t. Those biomarkers can then be used to predict who’s most at risk for chronic pain, and hopefully develop targeted, microbiome-directed treatments for helping those in pain feel better, says Aziz.

Using the GCPII Enzyme as Therapeutic Target

Barbara Slusher, Ph.D., the director of the Johns Hopkins Drug Discovery Program in Baltimore, has been studying a drug-like substance that can block an enzyme called GCPII. This enzyme, which is produced in both the brain and gut, makes neurons respond more readily to pain and is dramatically higher in IBD patients with inflammation.

As part of the Chronic IBD Pain Initiative, Slusher is looking to find out whether GCPII stays elevated in people with IBD whose pain lingers after remission. To do that, she and her team are conducting a study comparing tissue samples from patients with inactive IBD who are pain-free with samples from patients who continue to have pain in remission. “If we find that GCPII remains elevated specifically in patients with ongoing pain, it could provide important clues about why pain persists even after inflammation has improved,” says Slusher.

Should GCPII play a role in post-remission pain, it has the potential to lead to new treatment options. Slusher has already developed IBD3540, an oral GCPII inhibitor medication that’s been shown to reduce chronic visceral pain in preclinical animal trials published in the journal Gastroenterology. “If our current studies confirm that GCPII is elevated in IBD patients with persistent pain, it would provide strong support for developing IBD3540 as a targeted, non-opioid treatment for IBD pain,” Slusher says. “Importantly, this could represent one of the first therapies designed specifically to address the underlying biological mechanisms driving pain in IBD, rather than simply masking symptoms.”

Gut Bacteria, Lipids, and Diet

While targeted medications may be one way to address chronic pain, some experts suspect that certain dietary changes may also make a difference. At McMaster University in Hamilton, Ontario, Canada, Premysl Bercik, M.D., Ph.D., has been studying lipids (fat-like compounds) in the guts of people with IBD as well as in those with irritable bowel syndrome (IBS). He’s identified two lipids, lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), that trigger nerve pain, and which are present in higher concentrations in the stools of people with IBD and IBS who are experiencing severe pain. The findings were published earlier this year in the Journal of the Canadian Association of Gastroenterology.

LPC and LPA can be produced by bacteria in the gut when a person eats certain foods, including fatty meats, dairy, eggs, and soy, according to a 2024 study by Dr. Bercik that was also published in the Journal of the Canadian Association of Gastroenterology. With that knowledge, Dr. Bercik and his team are now tracking the pain symptoms of IBD patients for three weeks while closely monitoring their diet and measuring how much LPC and LPA are in their stool samples. “We hope to establish a clear link between severity of abdominal pain and levels of bacterial LPC and LPA, as well as to identify the specific dietary precursors and bacteria which produce these pain-inducing compounds,” he says. The study is also expected to wrap up towards the end of 2026.

Once that link is made, the next step will be developing tailored diets that can help keep LPC and LPA levels low in people with IBD who have chronic pain. “Further, we have identified probiotic bacteria which can degrade [LPC and LPA], so we can envisage a combined treatment: precision diet with specific probiotics,” Dr. Bercik adds.

Despite major treatment advances and the work of scientists like the ones above, chronic pain after remission remains one of the most persistent and poorly understood challenges in care for Crohn’s disease and UC. But the science is advancing at rapid pace. In just a few short years, researchers have learned that chronic abdominal pain reflects changes in how the gut, nervous system, and brain communicate with one another.

Even more significant, experts envision a future where personalized treatments can solve—and possibly even prevent—this all-too-common problem. “Our long-term goal is to develop both diagnostic tools and targeted therapies that improve the lives of patients who continue to suffer from chronic pain despite successful control of intestinal inflammation,” Slusher says.

As researchers uncover the various factors that can lead to post-remission pain, the hope is that physicians can treat it with precision medicine. “By characterizing [individual] pain patterns, symptoms, mental health, daily functioning, and linking that information to bio samples, microbiome differences, brain imaging, and metabolites, we can start to map distinct pain subtypes and pathways that are driving pain,” Hurtado-Lorenzo says. The result could be a future where living in remission could finally also mean living without chronic pain.