Summary: Inflammatory bowel disease (IBD) mainly occurs due to autoimmunity. So most drugs aim to tune the immune system. But a new study shows that people with weak or altered gut pain sensing may be more prone to IBD. Pain-sensing nerve cells that carry a protein called TRPV1 appear to also release substance P. Substance P shapes the gut bacteria, and that lowers inflammation.
Inflammatory bowel diseases (IBD) like ulcerative colitis and Crohn’s disease are severe gut inflammation. Autoimmunity (the body attacking itself) plays a key role in these diseases. Since it is the main cause of the inflammation, doctors use drugs that hold down immunity in the gut. But in many people, that is not enough. So researchers suspect they are missing something. There may be more to IBD than autoimmunity. People with IBD often must take drugs nonstop to prevent flares. Even so, some still have gut inflammation. It can cause severe ulcers and even a hole in the gut wall that needs surgery.
Researchers recently found something that gives hope for chronic pain treatment in people with IBD and gut pain. Nerve cells that sense pain in the gut can also guard it against inflammation and tissue damage. They do it by steering the gut bacteria. Also, gut neurons seem to release substance P that helps the gut microbiota, and so they can help reduce pain sensation. These findings come from new research by Weill Cornell University.
Science has long known two things. The gut has a huge web of nerves, more than anywhere outside the brain. And most of the body’s microbes live in the gut. Researchers now study how gut nerves and gut bacteria talk to each other. They want to know how that shapes IBD, gut health and inflammation. They found that people with IBD have fewer pain-sensing nerve cells, so they make less substance P. Genes seem to play a part. The researchers say this changes how we think about IBD. Up to now, science has mostly tried to tune immunity to fight IBD. These findings open the door to a whole new approach.
The nervous system seems to run the immune system more than we once thought. In this study, researchers looked closely at pain nerves in the gut. The tips of these nerves carry a protein called TRPV1. It plays a key role in pain signals and may help treat stomach inflammation. Heat, chili pepper, capsaicin and other things can switch it on. When researchers removed the gut nerves that carry TRPV1, gut inflammation got much worse. Tissue damage went up. But switching these receptors on had a protective effect.
Researchers also found that fewer pain receptors and less TRPV1 went along with less variety in gut bacteria. So they concluded that TRPV1 lowers gut inflammation by shaping the gut bacteria. It helps a healthier mix of bacteria grow. They also saw that nerve cells with TRPV1 released substance P. When given to mice with low TRPV1, substance P cut inflammation and boosted their gut bacteria.
Researchers concluded that the chain runs like this. Low TRPV1 and fewer pain-sensing nerve cells in the gut mean less substance P. Less substance P harms the gut bacteria. That brings more inflammation and worse outcomes in people with IBD. To check this, researchers also looked at gut tissue from people with IBD. They found lower TRPV1 and lower substance P. So these patients had faulty pain sensing, which may help drive chronic gut inflammation. How substance P shapes gut bacteria, and how nerves talk with gut microbes, is still unknown. Future studies need to answer that. Still, researchers propose that the next IBD drugs must target the nervous system.
Frequently asked questions
Do you have pain receptors in your gut?
Yes. The gut has a huge web of nerves, more than anywhere outside the brain. Some are pain-sensing nerve cells. Their tips carry a protein called TRPV1, which plays a key role in pain signals. TRPV1 can be switched on by heat, chili pepper, capsaicin and other substances. These same nerves turn out to do more than sense pain.
How do pain-sensing neurons help prevent gut inflammation?
Pain-sensing nerve cells that carry TRPV1 release substance P. It supports a richer, healthier mix of gut bacteria and lowers inflammation. In the study, removing these nerves made gut inflammation and tissue damage much worse. Switching them on had a protective effect. Giving substance P to mice with low TRPV1 reduced inflammation and boosted their gut microflora.
What causes inflammatory bowel disease?
Autoimmunity is the main driver of inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease. The Weill Cornell research adds a second piece. People with IBD have fewer pain-sensing nerve cells in the gut and make less substance P. That seems partly genetic. Their gut tissue showed lower TRPV1 and lower substance P. So faulty pain sensing may feed chronic gut inflammation.
Why don’t IBD medications always work?
Most IBD drugs work by holding down immunity in the gut. For many people that is not enough. They keep having inflammation even on drugs. Some end up with severe ulcers, a hole in the gut and surgery. The nervous system helps control gut immunity and gut bacteria. That is why researchers propose that the next IBD drugs should target the nervous system too.
Dr. Gurpreet Singh Padda, MD, MBA, MHP
