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A Promising Link Between Chronic Gut Pain and Anxiety

A new discovery into the link between the brain and chronic abdominal pain offers hope for improved treatments for anxiety and irritable bowel syndrome (IBS).

Chronic gut pain is commonly experienced by those with gastrointestinal disorders like IBS, which affects around 5% of children ages 4 to 18, and is often associated with anxiety and depression. Current treatments for gut pain are very limited, and women are twice as likely as men to be affected by IBS and report more fatigue, depression and anxiety with IBS.

A research team from UCSF and Flinders University in Australia has thus been investigating how the gut communicates with the nervous system. The team recently made a breakthrough finding, published in Nature, showing that a particular cell type on the lining of the gut, called EC cells, can directly send pain signals to the brain via the gut-brain axis, and these signals can be dampened to reduce both gut pain and anxiety.

“There is untapped potential in modulating this EC cell nerve circuit,” says James Bayrer, MD, PhD, first author of the study and UCSF Associate Professor of Pediatrics in the Division of Gastroenterology, Hepatology and Nutrition.

“Some of the next important steps will be to identify interventions that can dampen circuit activity and reduce pain,” says Bayrer.

Influence of the Gut

With IBS and other gastrointestinal disorders, pain can persist long after tissue damage has healed. The study suggests that chronic activation of EC cell circuits can cause lasting hypersensitivity and a susceptibility to continual pain.

Diet, stress and exercise can also all contribute to the development of hypersensitivity. “But patients who do not feel well often find it challenging and stressful to engage in healthy diet and exercise, causing a vicious cycle of maladaptive gut-brain communication,” says Bayrer.

Additionally, the study found that anxiety increases with activation of the EC cell circuit. For patients, this means that their chronic gut pain can last for an unknown amount of time and drive feelings of anxiety. For children in particular, this maladaptive cycle is very difficult to break and can lead to a lifetime of pain, anxiety and depression.

“We hypothesize that increasing or decreasing EC cell signaling can drive anxiety by pushing the gut-brain axis away from a calibrated baseline,” says Bayrer, whose team plans to research how exactly chronic gut pain can cause hypersensitivity.

Translating Research into Better Care

Bayrer says that the discovery that EC cells directly send pain signals to the brain allows for the development of drugs and interventions that block communication between the cells and nerves in the pathway. Silencing EC cells was particularly impactful in the study’s female mice, suggesting that modulating this circuit could greatly benefit women with chronic gut pain and related anxiety or depression.

“Our study reenforces the fundamental importance of considering sex in study design from basic bench work to clinical testing. Considering that chronic gut pain disproportionally affects women, investigating sex-based differences can lead to more effective, targeted therapies,” says Bayrer.

As clinical trials for chronic gut pain are rarely available for children and young adults, Bayrer hopes that this discovery can lead to protecting young people from the dangerous cycle caused by the link between chronic gut pain and anxiety.