What if pain is more than just a mere alarm bell? New research in mice illuminates how pain neurons shield the gut from damage. Pain is one of evolution's most effective mechanisms for detecting injury and letting us know that something is wrong. It acts as a warning system, telling us to stop and
Harvard Medical School researchers have analyzed the molecular crosstalk between pain fibers in the gut and goblet cells that line the walls of the intestine. The work shows that chemical signals from pain neurons induce goblet cells to release protective mucus that coats the gut and shields it from damage. The findings show that intestinal pain is not a mere detection-and-signaling system, but plays a direct protective role in the gut.
“It turns out that pain may protect us in more direct ways than its classic job to detect potential harm and dispatch signals to the brain. Our work shows how pain-mediating nerves in the gut talk to nearby epithelial cells that line the intestines,” said study senior investigator Isaac Chiu.
The experiments further showed that these receptors connect with a chemical called CGRP, released by nearby pain neurons, when the neurons are stimulated. These RAMP1 receptors, the researchers found, are also present in both human and mouse goblet cells, thus rendering them responsive to pain signals.
In addition to microbial presence, dietary factors also played a role in activating pain receptors, the study showed. When researchers gave mice capsaicin, the main ingredient in chili peppers known for its ability to trigger intense, acute pain, the mice’s pain neurons got swiftly activated, causing goblet cells to release abundant amounts of protective mucus.
“Pain is a common symptom of chronic inflammatory conditions of the gut, such as colitis, but our study shows that acute pain plays a direct protective role as well,” said study first author Daping Yang, a postdoctoral researcher in the Chiu Lab.The team’s experiments showed that mice lacking pain receptors also had worse damage from colitis when it occurred.