Pain-Sensing Neurons Help Prevent Gut Inflammation

January 30, 2023

Summary: Inflammatory bowel disease (IBD) mainly occurs due to autoimmunity. Thus, most medicines focus on modulating immune responses. However, a new study shows that those with altered or reduced gut pain sensation may be more prone to IBD. It appears that pain-sensing neurons expressing TRPV1 protein also secrete substance P. This substance P modulates gut microflora, thus reducing inflammation.

Inflammatory bowel diseases (IBD) like ulcerative colitis and Crohn’s disease are severe inflammatory conditions of the gut. It is known that auto-immunity plays a vital role in the development of these disorders.

Since auto-immunity is the prime cause of inflammation in IBD, doctors treat these conditions by using drugs that suppress local gut immunity. However, IBD treatment does not help sufficiently in many instances. This has led researchers to think that they might be missing something. There could be more to IBD than mere autoimmunity. People living with IBD often have to take medications to prevent flares continually. Unfortunately, some people continue to experience gut inflammation even with drug therapy, causing severe gut ulcers and even perforation, thus requiring surgical intervention.

Recently, researchers made an exciting observation providing hope for chronic pain treatment in those living with IBD and gut-related pain. They found that neurons that sense pain in the gut can also help protect the gut from inflammation and tissue damage by regulating gut microflora. In addition, it appears that gut neurons secrete a substance P that has a beneficial impact on gut microbiota, and thus they can help reduce pain sensation. These are the findings of the latest research by Weill Cornell University1.

Science has long known a few things such as the gut having an extensive neural network and the most neurons outside the brain, as well as most of the microbiota residing in the gut. Researchers are now exploring the interaction between gut neurons and microflora, and its role in the development of IBD, especially in terms of gut health and inflammation.

The researchers found that pain-sensing neurons are diminished in those living with IBD, thus lowering the production of substance P. This also appears to have something to do with genetics. Researchers say that these findings transform our thinking about IBD. To date, science has been mostly focusing on modulating immunity to counter IBD. However, these findings open perspectives for a whole new approach.

The nervous system appears to be more important in regulating the immune system than imagined earlier. In the present study, researchers particularly examined pain neurons in the gut. The endings of these neurons express a protein called TRPV1, which plays a vital role in pain signaling and has potential for use in stomach inflammation treatment. This protein can be activated by heat, chili pepper, capsaicin, and other substances. Researchers found that deleting the gut nerves that express TRPV1 results in much worse gut inflammation and increased tissue damage. But on the other hand, activating these receptors have a protective effect.

Further, researchers found that reduced pain receptors and lesser TRPV1 expression were related to reduced gut microflora diversity. Hence, they concluded that TRPV1 helps reduce gut inflammation by influencing the gut microflora. As a result, it promotes a healthier population of gut bacteria. Further, researchers also noticed that TRPV1-expressing neurons secreted a protein P. When given to mice with low TRPV1 expression, this substance was good at reducing inflammation and boosting gut microflora.

Hence, researchers concluded that low expression of TRPV1 and a lower population of pain-sensing neurons in the gut results in low substance P production. This negatively impacts the gut microflora, resulting in higher inflammation and poor outcomes in those living with IBD. To confirm their finding, researchers also examined the gut tissues of people living with IBD and found lower expression of TRPV1 and lower substance P. It means that these patients had disrupted pain sensations, which may be one of the contributing factors to chronic gut inflammation. How substance P influences the gut microflora and how the nervous system talks with gut microbes remain unknown, and it should be the subject of future studies. Nonetheless, researchers propose that new-generation IBD drugs must focus on targeting the nervous system for managing IBD.

By Gurpreet Singh Padda, MD, MBA, MHP