Are painkillers bad for your gut?

Pain is our body’s way of telling us something is wrong, alerting us to an injury or infection, and helping doctors make a diagnosis. But pain is not fun, so we often try to block it with drugs.

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

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

In the study, pain neurons in mice helped regulate the protective mucus that lines the gut, releasing more mucus in response to inflammation.

“These neurons signal to goblet cells in the gut that make mucus,” says lead study investigator Isaac Chiu, PhD, associate professor of immunobiology at Harvard’s Blavatnik Institute. “This is very important because mucus protects the gut from potentially harmful microbes and tissue damage.”

Messing up that process could lead to dysbiosis, an imbalance in the gut, paving the way for inflammation and increasing the risk of painful bowel conditions like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), says Chiu.

What the scientists did

In the study, researchers bred mice that lacked pain neurons. These mice produced less protective mucus, and “their gut microbiota became dysregulated,” Chiu says. “They also became more susceptible to colitis” (inflammation of the intestines characterized by stomach pain and bowel movements).

To find out why, the researchers looked at these mucus-forming goblet cells. They discovered 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 nociceptive neurons in response to pain.

Without that CGRP or those receptors, the gut won’t get the message to produce more mucus – and mucus production is reduced.

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

Of particular concern is the class of migraine medications that suppress CGRP, Chiu says.

“If we target CGRP long-term, it could cause defective gut lining, including loss of good microbes and increased susceptibility to inflammation,” he says.

What’s more, given that painkillers are often used to treat patients with colitis, the potential adverse effects may be important, the researchers say.

Why this matters

The study builds on growing research into “organ communication,” how molecules in the body communicate between organs to help us maintain health. It highlights the gut-brain axis, a signal between the gastrointestinal tract and the central nervous system.

“Acute pain is designed to protect us from damage, so it makes sense that it could be linked to mucus secretion,” says Chiu. “If we lose this signal, we are 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 the other side of the coin,” says Chiu. “We need to find ways to keep the good side of pain signals, like maintaining gut balance, and block the perception of pain in the brain, which is the part that causes people to suffer.”

That means better understanding the things that control pain signals in the gut, so we can “tune it down” without turning it off completely, he says.

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

In the meantime, improving your gut health can help manage the pain signaling process, says Chiu. Healthy microbes can stimulate pain fibers enough to maintain mucus without contributing to the gut. You can feed healthy gut microbes by eating more fiber and fermented foods and cutting back on fried foods and red meat. Exercise, managing stress and getting outside can also help.

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