A global research collaboration has revealed how certain gut cells switch on pain signals, which can linger long after the initial trigger has passed, potentially contributing to chronic pain in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).

The study, published in Nature, found that special gut cells, called enterochromaffin (EC) cells, play a more significant role in pain than previously thought, by detecting harmful stimuli and releasing large amounts of neurotransmitters that influences how nerves communicate with the brain.

The paper was led by SAHMRI’s Professor Stuart Brierley, Nobel Laureate Professor David Julius and Dr Kouki Touhara from the University of California San Francisco (UCSF), and Professor Yulong Li from Peking University.

The researchers identified two key types of EC cells that respond to different gut conditions. One type, known as villus EC cells, is found higher up in the gut lining, and acts as an early warning system by detecting harmful stressors, such as oxidative damage. When activated villus EC cells release serotonin along with another molecule called ATP, which activate nerve pathways that send pain signals to the brain.

“Villus EC cells act like guards, releasing both serotonin and ATP as an alarm system for the body, alerting it that there’s a problem in the gut,” Prof Brierley said.

“The second type of EC cell, called crypt EC cells, is located deeper in the gut lining. When the gut’s protective barrier is weakened, they respond to irritants, such as certain compounds found in spicy foods like wasabi and mustard and release serotonin which acts on nerves to signal pain.

“Normally, these crypt EC cells help regulate secretions in the gut, aiding digestion, but when they are exposed to harmful irritants or during inflammation, they flood the system with serotonin thereby activating nerves, and triggering discomfort or pain,” Prof Brierley said.

By better understanding how these gut sensors interact with the nervous system, researchers hope to develop new treatments that target pain at its source.

“We now have a much clearer picture of how gut pain is generated and maintained,” Prof Brierley said.

“If we can find ways to regulate how EC cells are activated it could be instrumental in finding more effective treatments for chronic gut pain, which affect millions of people around the world”.

This research was supported by funding from the National Health and Medical Research Council (NHMRC) of Australia and the US National Institutes of Health.

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