Gut-innervating nociceptors found to regulate the intestinal microbiota and promote tissue protection Cornell Nociceptors IntestinalMicrobiota Microbiota TissueProtection
By Nidhi Saha, BDSOct 19 2022Reviewed by Aimee Molineux According to a recent study published in Cell Reports, substance P produced by the nociceptors in the gut lining confers protection against inflammation and tissue damage by increasing the number of beneficial microbes.
Several inflammatory disorders, including inflammatory bowel diseases , rheumatoid arthritis, and multiple sclerosis, cause distress, impair quality of life, and precipitate chronic pain. Pain sensation is triggered to warn against tissue damage or injury. The present study investigated the innervation of TRPV1+ nociceptor cells in the intestines of mice and their functioning during homeostasis and inflammation. This study evaluated the vulnerability of TRPV1+ nociceptors in mice injured and inflamed in the intestine by utilizing targeted chemogenetic silencing, adenoviral-mediated colon-specific silencing, or pharmacological ablation.
A chemogenetic strategy to acutely silence TRPV1‑ nociceptors in vivo by producing TRPV1hM4Di mice in which TRPV1+ nociceptors express the inhibitory designer receptors were exclusively activated. The colon substance P and CGRP levels in mice treated with DSS, DMSO, or RTX. The clinical disease score, colon length, H&E staining, and daily weight loss of the distal colon were used to track the disease and recovery of DSS-treated DMSO- or RTX-treated Tac1/mice.
When TRPV1+ nociceptors are transiently silenced or permanently ablate, changes in the intestinal microbiota occur and transplantation of microbes from mice with dysregulated nociception worsens intestinal injury and inflammation. It has been shown that TRPV1+ nociceptor-mediated tissue-protective actions are associated with Gram+ bacterial modifications, and selective colonization of germ-free mice with Gram positive Clostridium species enhances tissue protection.
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