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huh_phd t1_isayrlt wrote

Back to back posts with IBD relevant research. Hooray! It is crohns and colitis awareness month after all

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Snaz5 t1_isasguc wrote

yeah but will it make me feel like ive been punched in the stomach everytime i eat too big a dinner? actually maybe that's a good idea for different reasons

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AlbertVonMagnus t1_iscc791 wrote

Abstract:

>Neuroepithelial crosstalk is critical for gut physiology. However, the mechanisms by which sensory neurons communicate with epithelial cells to mediate gut barrier protection at homeostasis and during inflammation are not well understood. Here, we find that Nav1.8+CGRP+ nociceptor neurons are juxtaposed with and signal to intestinal goblet cells to drive mucus secretion and gut protection. Nociceptor ablation led to decreased mucus thickness and dysbiosis, while chemogenetic nociceptor activation or capsaicin treatment induced mucus growth. Mouse and human goblet cells expressed Ramp1, receptor for the neuropeptide CGRP. Nociceptors signal via the CGRP-Ramp1 pathway to induce rapid goblet cell emptying and mucus secretion. Notably, commensal microbes activated nociceptors to control homeostatic CGRP release. In the absence of nociceptors or epithelial Ramp1, mice showed increased epithelial stress and susceptibility to colitis. Conversely, CGRP administration protected nociceptor-ablated mice against colitis. Our findings demonstrate a neuron-goblet cell axis that orchestrates gut mucosal barrier protection.

Capsaicin produced the effect, though not directly on the TRPV1 (aka "capsaicin/vanilloid receptor"). But this suggests that TRPV1 is likely the "nociceptor" being described here, and CGRP is produced downstream which then mediates the rest of the effect (likely including pain)

CGRP is believed to be the major downstream mediator of migraines, as CGRP inhibitors (receptor antagonists) tend to provide faster relief of symptoms than 5-HT1B / 5-HT1D agonists like the tryprans which reduce CGRP production but don't block the already existing CGRP from their receptors. Whether or not CGRP from the gut can contribute to migraine would be an interesting subject for future study, as gut problems are known to be fairly comorbid with headaches

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TheBargoyle t1_isegkt0 wrote

As someone with a capsaicin addiction (e.g. my last meal was a sandwich of just five habaneros, spicy hummus, and ghost pepper condiment), a history of migraines, and a neurobiology education, your analysis feels like a targeted ad. Thank you for the insight and the prompt to do a little more digging in the literature on the subject!

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AlbertVonMagnus t1_isfsx6q wrote

Ah I see you're a man of culture as well. I usually add a little meat to my habanero sandwich for some protein though, and ghost pepper cheese. Dairy emulsifies the capsaicin nicely

Always happy to share my thoughts on neurobiology. Let me know if you learn anything interesting

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hardtofindagoodname t1_ise0b9d wrote

Anyone can ELI5? Does this mean eating green chilli's will have this effect?

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elfjan t1_isfapv4 wrote

Pain-sensing neurons called nociceptors relay signals to the brain and spinal cord to tell us when they detect harmful stimuli – for example, when we eat capsaicin (the spicy compound in chili peppers) or experience mechanical stretch.

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