# The role of mucosal serotonin in visceral nociception and gut motility

> **NIH NIH F32** · NEW YORK UNIVERSITY · 2022 · $67,582

## Abstract

PROJECT SUMMARY/ABSTRACT
 Irritable bowel syndrome (IBS) is a highly prevalent disorder characterized by visceral pain and dysmotility.
IBS causes substantial morbidity in children and adults and current therapy is inadequate. Serotonin (5-HT)
signaling plays roles in pain and motility, but the efficacy of modifying 5-HT signaling to treat IBS is limited and
fraught with adverse effects. A greater understanding of how enteric 5-HT contributes to IBS pathophysiology
may therefore provide for novel and effective treatments for the condition. Enterochromaffin (EC) cells in the
gastrointestinal (GI) epithelium produce most of the 5-HT in the gut, which is thought to stimulate extrinsic primary
afferent neuron (ExPAN) and intrinsic primary afferent neuron (IPAN) terminals to promote sensory and motor
signaling, respectively. The serotonin reuptake transporter (SERT), present throughout epithelial cells, rapidly
inactivates 5-HT. Selective serotonin reuptake inhibitors (SSRIs) inhibit SERT and thus increase 5-HT availability
for IPAN and ExPAN stimulation. Despite their use for pediatric IBS, SSRIs are often ineffective and plagued by
adverse GI effects, which may be due to their effects at sites other than the GI epithelium. My prior and
preliminary data strongly suggest that epithelial-restricted 5-HT modulation may limit unwanted effects and thus
improve therapy. My data also show a novel visceral pain mechanism involving SERT regulation of mucosal 5-
HT. In the current proposal, I will investigate the effects of epithelial 5-HT on GI motility and visceral nociception
using optogenetic tools that induce or inhibit EC cell secretion, mouse lines that either lack mucosal 5-HT or
SERT, and pharmacological interventions that alter mucosal 5-HT signaling. The proposed research strategy
will allow me to test the hypotheses that 1) 5-HT released from EC cells and 2) SERT-mediated regulation of
mucosal 5-HT availability modulate visceral nociception and GI motility.

## Key facts

- **NIH application ID:** 10535862
- **Project number:** 1F32DK132810-01A1
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Sarah Najjar
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2022-09-07 → 2025-09-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535862

## Citation

> US National Institutes of Health, RePORTER application 10535862, The role of mucosal serotonin in visceral nociception and gut motility (1F32DK132810-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10535862. Licensed CC0.

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