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November 16, 2022 Pain is our body’s way of telling us something is wrong, alerting us to injury or infection, and helping doctors make a diagnosis. But pain is no fun, so we often try to block it with medication.

But a surprising one new study led by researchers at Harvard Medical School suggests that blocking acute pain may actually lead to gut pain.

That’s because pain can be an important part of a process that protects the gut from damage.

In which to learnpain neurons in mice helped regulate the protective mucus lining the gut and released more mucus in response to inflammation.

“These neurons signal the goblet cells in the gut, which produce mucus,” says the study’s lead investigator Isaac Chiu, PhD, Associate Professor of Immunobiology at the Blavatnik Institute at Harvard. “This is very important because mucus protects the gut barrier from potentially harmful microbes and tissue injury.”

Playing with this process could lead to dysbiosis, an imbalance in the gut that paves the way for inflammation and increases the risk of painful gut conditions like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), Chiu says.

What the researchers did

In the study, the researchers bred mice that lacked pain neurons. These mice produced less protective mucus, and “their gut microbiome became dysregulated,” says Chiu. “They also became more prone to colitis” (Inflammation in the gut, characterized by abdominal pain and bowel problems).

To find out why, the researchers took a close look at these mucus-producing goblet cells. They found that the cells contain a receptor called RAMP1 that helps them respond to pain. This receptor is activated by a neuropeptide called CGRP, which is released by pain neurons in response to pain.

Without this CGRP or these receptors, the gut won’t get the message to produce more mucus—and mucus production will decrease.

“We need this signal to maintain a healthy gut,” says Chiu.

Of particular concern is a class of migraine drugs that suppress CGRP, Chiu notes.

“If we target CGRP long-term, it could result in compromised gut mucosal health, including loss of good microbes and increased susceptibility to inflammation,” he says.

Additionally, given that pain relievers are commonly used to treat patients with colitis, it may be important to consider the potential harmful effects, the researchers say.

Why this matters

The study builds on growing research into “communication between organs,” how molecules in the body interact between organs to help us maintain health. It sheds light on the gut-brain axis and signals between the gastrointestinal tract and the central nervous system.

“Acute pain is designed to protect us from harm, so it makes sense that it might be coupled with the secretion of mucus,” says Chiu. “If we lose that signal, we’re more likely to have an injured or inflamed gut.”

On the other hand, too much pain signaling is probably not helpful either.

“Chronic pain is on the other side of the coin,” says Chiu. “We need to find ways to preserve the good aspects of pain signaling, such as B. maintaining gut homeostasis, and turning off pain perception in the brain, which is the part that makes people suffer.”

That means a better understanding of the things that control pain signals in the gut so we can “curl them down” without shutting them off entirely, he says.

More research is needed to confirm the results in humans. But depending on how the research develops, it could change the way we deal with pain and open the door to new treatments for patients with bowel diseases, says Chiu.

Meanwhile, improving your gut health can help regulate the pain signaling process, Chiu notes. Healthy microbes can stimulate pain fibers just enough to maintain mucus without contributing to gut pain. You can feed Healthy Gut Microbes by eating more fiber and fermented foods and reducing fried foods and red meat. Exercise, stress management, and getting outside can also help.



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