Pain in the Gut May have a Reason

Activation of gut pain receptors activates goblet cells that secrete healthy mucus which helps maintain a healthy gut microbiome. Research in mice points to this contribution.

Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection. Daping Yang et al; Cell Oct 2022

Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection.
Daping Yang et al;
Cell Oct 2022 in press

I got much info from:

Gut pain may help to maintain a healthy microbiome in mice
New Scientist

  • CGRP neurotransmitter pain receptors are the ones that secrete healthy gut mucous and genetically bred to not have this will induce inadequate protection and a thinner mucous cell lining.
  • CGRP receptors are big news as blocking of these in migraines is a newer treatment for headaches

Comment – now to design it so not need so much protection!

Back in the 1970’s, increased inflammatory prostaglandins were found in stools of patients with irritable bowel syndrome (IBS). At the time, this disorder was considered completely psychological, so when I brought up this inconsistency in a lecture, I was ignored. Now it looks like an inflammatory/pain process is underway. This pain process attracts mast cells and three times the mast cell content in gut lining is typical in IBS:

O’sullivan, M., et al.
Increased mast cells in the irritable bowel syndrome.
Neurogastroenterology and Motility 12.5 (2000): 449-458.

Blocking CGRP receptors done with new antimigraine CGRP antibody meds leads to abdominal problems:
Falkenberg, Katrine, Helene Rønde Bjerg, and Jes Olesen.
Two‐Hour CGRP Infusion Causes Gastrointestinal Hyperactivity: Possible Relevance for CGRP Antibody Treatment.
Headache: The Journal of Head and Face Pain 60.5 (2020): 929-937.
“Rumbling, stomach pain, nausea, diarrhea, and an urge to defecate were the most commonly experienced GI side effects”

Bacteria can activate Gut sensory neurons:

Chiu, Isaac M., et al.
Bacteria activate sensory neurons that modulate pain and inflammation.
Nature 501.7465 (2013): 52-57.

How little we know about bacteria has been demonstrated by finding previously undetected bacteria in prostate cancer:
Hurst, Rachel, et al.
Microbiomes of urine and the prostate are linked to human prostate cancer risk groups.
European Urology Oncology Vol. 5 Issue 4 p412–419


they put it:

“At least five types of bacteria, some previously unknown to science, have been found in the urine of men with an aggressive form of prostate cancer, researchers have announced.”

probiotics help so gut microbiome is important…

This note will have to be updated as new discoveries are made…

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