PainRelief.com: What are the main findings?
Response: We first looked in mice that lacked pain fibers and found that mucus was much thinner than in regular mice. We also found that these mice had dysregulated gut microbiome. We also found that if we specifically activated pain fibers in the gut, this led to immediate increases in mucus production. We hypothesized that pain fibers may be talking to goblet cells directly to induce mucus secretion. We found that one specific molecule called CGRP which is produce by pain fibers acted on goblet cells through its receptor RAMP1, which caused goblet cells to empty their contents and secrete mucus. We used epithelial organoids to also show this can happen in a dish. We then found that capsaicin, the ingredient in chilli peppers that make foods spicy, can act on pain fibers in the gut, cause CGRP to go up, and mucus levels to increase in the gut. Another stimulus we found was the gut microbiome, and we found that pain fibers would secrete CGRP in response to microbial stimuli.
Finally, since mucus is important for protecting the gut barrier, we tested if mice lacking pain have more susceptibility to damaging molecules that cause colitis or gut inflammation. Indeed we found that mice lacking pain fibers got more severe inflammation when we induced colitis, and that if we give these mice CGRP it restored their protection.
PainRelief.com: What should readers take away from your report?
Response: Our data shows that pain in the GI tract is coupled to mucus production. This is protective because it could help the body remove harmful substances that stimulate pain. We also found that lacking pain could be negative in that it made mice more susceptible to colitis. Patients who are being treated for migraine using drugs that block CGRP or its signaling should be a bit wary if this could potentially dysregulate the gut, disrupting mucus levels, the microbiome and even make them more susceptible to inflammation. We should therefore study if these are consequences in the guts of these patients.
PainRelief.com: What recommendations do you have for future research as a result of this study?
Response: Future research is needed to find out what are the different stimuli in the gut, including from the microbiome, that regulates pain fiber activation, CGRP levels and mucus production. We also need to understand whether people who take pain-modulating medicines have negative consequences on gut mucus levels and barrier protection.
Disclosures include that we are collaborating with some companies like Moderna and Abbvie to find ways to target neurons and pain.
Daping Yang, Amanda Jacobson, Kimberly A. Meerschaert, Joseph Joy Sifakis, Meng Wu, Xi Chen, Tiandi Yang, Youlian Zhou, Praju Vikas Anekal, Rachel A. Rucker, Deepika Sharma, Alexandra Sontheimer-Phelps, Glendon S. Wu, Liwen Deng, Michael D. Anderson, Samantha Choi, Dylan Neel, Nicole Lee, Dennis L. Kasper, Bana Jabri, Jun R. Huh, Malin Johansson, Jay R. Thiagarajah, Samantha J. Riesenfeld, Isaac M. Chiu,
Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection,
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Last Updated on October 16, 2022 by PainRelief.com