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Inflammation and Pain-Sensing Gut Neurons

Updated: Nov 20, 2022

Research update! Be forewarned that this article is dense! Long story short is that nerve cells in our gut that experience pain may be playing more of a role than creating discomfort. The studies are showing that pain neurons play have a protective role against inflammation.

Two studies conducted by different teams at Harvard Medical School and Weill Cornell Medicine, published in the journal Cell, suggest that pain-sensing neurons in the gut can help protect against inflammatory damage. This means that these neurons might have more than one job!

The team from Harvard Medical School researched how pain neurons communicate with goblet cells in the gut. Goblet cells are special cells that line the intestine and secrete mucus when they detect inflammation. Scientists knew that the pain-sensing neurons must also send a signal to other gut cells indicating there was a problem, but they didn't know exactly how it worked.

The researchers conducted experiments with mice to learn more about pain. They found that goblet cells have special receptors. These receptors are able to detect when the pain neurons are sending a message. The pain neurons send out a chemical called calcitonin gene-related peptide (CGRP). This chemical causes the goblet cells to secrete mucous.

Scientists found that when you feel pain or something is wrong, a chemical called CGRP turns on. This chemical helps to keep the good microbes in your gut healthy so everything can stay in balance. The researchers found that getting rid of the body's natural pain response may have harmful consequences. They looked at mice who did not have pain neurons in the gut or CGRP receptors and observed more severe damage from inflammation.

The team at Weill Cornell Medicine studied a specific receptor called TRPV1. This receptor is what causes the burning pain in your stomach if you have an inflammatory bowel condition, such as IBS. However, they found that silencing these receptors completely actually makes gut inflammation worse.

The research found that the pain-sensing response did more than just send information to the brain. Further research found that animals without the TRPV1 gene had different populations of gut bacteria, which caused more inflammation and damage. When researchers blocked TRPV-1 in mice, it had bad effects on the gut bacteria.

The good news is that these negative effects could be reversed simply by giving the animals Substance P directly which is a molecule secreted by TRPV-1. This research also found that some types of bacteria can actually help to activate the secretion of Substance P from gut nerves.

These studies are investigating how the nerves in our stomachs affect inflammatory diseases. This is new and exciting research & could lead to new discoveries! Hopefully, these studies can help us understand chronic inflammation and possibly help us come up with new anti-inflammatory treatments to target these gut neuron mechanisms.


Zhang, W., Lyu, M., Bessman, N. J., Xie, Z., Arifuzzaman, M., Yano, H., Parkhurst, C. N., Chu, C., Zhou, L., Putzel, G. G., Li, T.-T., Jin, W.-B., Zhou, J., Hu, H., Tsou, A. M., Guo, C.-J., & Artis, D. (2022). Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection. Cell, 185(22).

Yang, D., Jacobson, A., Meerschaert, K. A., Sifakis, J. J., Wu, M., Chen, X., Yang, T., Zhou, Y., Anekal, P. V., Rucker, R. A., Sharma, D., Sontheimer-Phelps, A., Wu, G. S., Deng, L., Anderson, M. D., Choi, S., Neel, D., Lee, N., Kasper, D. L., … Chiu, I. M. (2022). Nociceptor neurons direct goblet cells via a CGRP-ramp1 axis to drive mucus production and gut barrier protection. Cell, 185(22).


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