People with inflammatory bowel disease (IBD) often suffer from abdominal pain outside of acute inflammatory flare-ups, which could be related to altered processing of pain in connection with fear. A research team at Ruhr-Universität Bochum has now found in a study that IBD patients feel pain more intensely and unpleasantly if they have previously learned pain-related fear. The results point to central adaptations in the brain and argue for personalized therapies that include psychological mechanisms. The work was published in the journal Pain on November 26, 2025.

Chronic inflammatory bowel diseases such as ulcerative colitis affect millions of people and cause recurring pain that lasts beyond acute inflammation. Researchers suspect that emotional factors such as fear play a role, as pain signals potential tissue damage and leads to learning processes in which sufferers avoid stimuli associated with discomfort. In other chronic pain conditions, such as irritable bowel syndrome, patients are known to internalize pain-related anxiety to a greater extent, which increases and maintains pain. The Bochum study investigated whether similar processes are effective in IBD.

The team led by Hanna Öhlmann from the Center for Medical Psychology and Translational Neurosciences recruited 43 subjects: 21 patients with dormant ulcerative colitis, with an average of 13.5 years, and 22 healthy controls of comparable age. The participants were mostly female, with an average age of about 46 years. Exclusion criteria included extreme age groups, a body mass index outside of 18 to 30, psychiatric comorbidities in IBD patients, and recent use of immunosuppressants or corticosteroids. The study was conducted between July 2019 and March 2020.

In a two-day experiment, a differential fear-conditioning paradigm was applied. On the first day, the test subjects saw symbols on a screen: one symbol was repeatedly associated with a painful heat stimulus on the lower abdomen, another was not. In this way, they learned which symbol announced pain. This was followed by an extinction phase, in which all symbols were presented without stimuli in order to reduce the learned fear. On the second day, extinction was repeated, followed by unexpected re-exposure to the heat stimuli without visual cues. Pain perception was assessed using visual analogue scales for intensity and discomfort. In addition, inflammatory markers such as TNF-alpha, IL-6, CRP, white blood cells, calprotectin and lactoferrin as well as neuroendocrine markers such as cortisol and salivary amylase were measured. Statistical evaluations used robust methods such as Yuen-t tests, mixed ANOVAs, correlations and mediation analyses.

The IBD patients reported more gastrointestinal symptoms and higher pain-related anxiety and catastrophization compared to the healthy ones, but showed no differences in overall pain sensitivity or thresholds. Both groups successfully learned and extinguished fear, without group-specific deviations. However, during re-exposure, IBD patients felt the pain significantly more intense and uncomfortable. In this group, the extent of learned pain-related fear from the first day correlated with the perception of pain on the second day: higher fear was associated with greater intensity and unpleasantness. Mediation analyses showed that this connection was completely mediated by the perceived unpleasantness, which emphasizes the emotional component of the pain. Such correlations were missing in the healthy people.

The results suggest that in IBD it is not the learning of fear itself that is enhanced, but the way in which fear modulates the perception of pain. This could be due to central adaptations in the brain caused by recurrent inflammatory flare-ups. Previous studies have found structural and functional changes in brain regions that process fear and pain. The study identifies fear-induced hyperalgesia as a mechanism for persistent pain in resting phases, consistent with nociplastic pain concepts in which central sensitization plays a role.

Previous treatments for IBD have focused on controlling inflammation in the digestive tract. However, the researchers call for recognition of chronic abdominal pain as a central disease feature and the integration of psychological factors such as stress, avoidance and fear. Patients who are in pain despite inflammation-free phases could benefit from holistic approaches. Studies on psychological interventions, such as cognitive behavioral therapy, that address fear and avoidance are recommended. Such methods could also be used for other inflammatory diseases with pain, such as rheumatism or endometriosis. The study highlights the need for personalized therapies that take emotional reactivity into account to fill gaps in pain management.

The work was funded by the German Research Foundation, specifically within the framework of the Collaborative Research Centre 1280 on Extinction Learning under project number 316803389. Ruhr-Universität Bochum is considered a leading centre for neuroscience and medical psychology, where interdisciplinary teams research the mechanisms of chronic diseases. These findings could transform clinical practice by broadening the focus from purely drug to integrated treatments. In Germany, an estimated 400,000 people suffer from IBD, and persistent pain puts a significant strain on their lives. By taking emotional factors into account, the quality of life could be improved and the burden on the health system could be relieved. The study contributes to the growing evidence that psychological processes play a key role in somatic diseases and should be used therapeutically.

Original Paper:

PAIN

Editor: X-Press Journalistenbüro GbR

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