What if the sensation of pain is more than simply a simple warning sign? What if suffering is, in and of itself, a defense mechanism? That may very well be the case with mice, according to the findings of a recent study that was headed by experts at Harvard Medical School. This study, which was published on October 14 in the journal Cell, demonstrates that pain neurons in the mouse gut control the existance of protective mucus under normal circumstances and drive intestinal cells to generate more mucus during inflammatory situations.
The research provides a step-by-step breakdown of a complicated signaling chain and demonstrates that gut cells that carry mucus and are known as goblet cells participate in direct communication with pain neurons. It seems that pain may safeguard us in more obvious ways than its traditional role of detecting possible damage and sending messages to the brain. Research demonstrates how neurons that control pain in the digestive tract communicate with neighboring epithelial cells that coat the intestines. This suggests that the nervous system plays a far more significant function in the gut than just providing us with an unpleasant feeling, and that it is an essential component in the maintenance of the gut barrier as well as a protective mechanism when there is inflammation.
Goblet cells are found in both the intestines and the airways of humans. Goblet cells, so called for their cup-like shape, are filled with a mucus that has the consistency of a gel and is composed of proteins and carbohydrates. During a series of tests, the researchers noted that mice without pain neurons generated less protective mucus and had alterations in their intestinal microbial makeup. This condition is known as dysbiosis, and it is characterized by an imbalance between helpful and dangerous microorganisms. The researchers examined the function of goblet cells both in the presence and the absence of pain neurons in order to get a better understanding of how exactly this protective crosstalk takes place.
Results
They discovered that the surfaces of goblet cells contain a type of receptor that is referred to as RAMP1. This receptor ensures that the cells can respond to adjacent pain neurons, which are activated by dietary and microbial signals, as well as mechanical pressure, chemical irritation, or drastic changes in temperature. The investigations also shown that these receptors communicate with a protein known as CGRP, which is generated by neighboring pain neurons when the neurons are triggered. This chemical was found to be responsible for the release of the receptors. According to the findings of the researchers, these RAMP1 receptors are also present in the goblet cells of both humans and mice, which enables the goblet cells to respond to pain signals.
In addition, the experiments demonstrated that the presence of certain gut microorganisms stimulated the production of CGRP, which helped to preserve the homeostasis of the gut. According to the results,,the activation of pain receptors was caused not only by the presence of microbes but also by dietary variables. When scientists decided to give mice capsaicin, the primary component in chili peppers that is known for its ability to trigger intense and acute pain, the mice’s pain neurons were quickly activated, which caused goblet cells to secrete bountiful quantities of protective mucus. This was discovered after the scientists gave the mice capsaicin.
On the other hand, mice who lacked pain neurons or goblet cell receptors for CGRP were more prone to developing colitis, a kind of inflammation that occurs in the stomach. The discovery may help to explain why those who have gut dysbiosis may have an increased risk of developing colitis. The researchers saw a dramatic improvement in mucus production in the mice when they administered CGRP, a pain-signaling protein, to the animals that lacked pain neurons. Even though the mice did not have any pain neurons, the therapy was nevertheless able to protect them against colitis.
