Pain-sensing neurons provide protection against gut inflammation and tissue damage associated with it. According to a study by researchers of Weill Cornell Medicine, the neurons regulate the microbes living in the intestines.
The report by the researchers is in Cell and it found in a preclinical model that the gut’s pain-sensing neurons secrete substance P. This molecule called substance P protects the gut from inflammation and tissue damage linked with it. They boost the number of beneficial microbes in the gut. Furthermore, researchers also found that when pain-signalling genes disrupt, the pain-sensing nerves diminish. This is very common in people who have inflammatory bowel disease.
Senior author Dr. David Artis said,
These findings reshape our thinking about chronic inflammatory disease, and open up a whole new approach to therapeutic intervention,
The first author of the study Dr. Wen Zhang further added,
Defining a previously unknown sensory function for these specific neurons in influencing the microbiota adds a new level of understanding to host-microbiota interactions.
Regulation of Gut Inflammation
Chron’s disease and ulcerative colitis, both are covered under IBD. Moreover, it affects millions in the United States and is treated with drugs that target elements of the immune system directly. Hence, now, scientists appreciate the regulation of gut inflammation through gut-dwelling bacteria and other microbes.
Additionally, it has been shown in recent years that the nervous system relates to most organs. Therefore, it is another strong regulator of the immune system at the body’s barrier. Dr. Artis, along with his team especially studied pain neurons that extend to the gut.
The gut-innervating pain neurons express a protein called TRPV1. It serves as a receptor for pain signals and is activated by high heat and acid. For example, the brain translates it into burning pain. Researchers revealed that TRPV1 receptors are silenced in the gut nerves, or if TRPV1-expressing neurons are deleted, it makes inflammation worse. Additionally, it also causes tissue damage. Whereas activating these effects can have a protective effect.
Furthermore, scientists found strong evidence that most of the TRPV1-expressing nerves come from substance P. They also observed that it can reverse the most harmful effects of blocking TRPV1. Additionally, experiments confirmed the signalling between microbes was two ways. Some of the bacterial species can activate TRPV1 expressing nerves for them to produce substance P.
Hence, to confirm this relevance gut tissues of IBD patients were examined. The researchers found abnormal TRPV1 and substance P gene activity. Moreover, they also found overall few signs of TRPV1 as well.
Dr Zhang said,
These patients had disrupted pain-sensing nerves, which may have contributed to their chronic inflammation,
Conclusion
Substance P affects the gut microbe population and how they react back. Ongoing studies are being conducted to answer these queries. However, so far, the results suggest that the next generation of anti-inflammatory drugs for IBD and other disorders can be nervous system-targeting compounds.
Dr. Artis says,
A lot of current anti-inflammatory drugs work in only some patients, and pharma companies really haven’t known why,
Maybe it’s because, when it comes to chronic inflammation, we’ve been seeing only some of the picture—and now the rest, including the role of the nervous system, is starting to come into focus.
