# Mapping gut-spinal cord connections in visceral pain

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $795,511

## Abstract

Project Summary/Abstract
 Our current understanding of mechanisms underlying visceral pain, including that associated with irritable
bowel syndrome, remains rudimentary. Importantly, opiates are ineffective at treating visceral pain syndromes,
and only exacerbate discomfort by producing constipation, reflecting a clear need for alternative treatment
options. The goal of this proposal is to bring greater mechanistic insight to this underserved area of pain research,
and to approach the problem in a multifaceted strategy designed to maximize the relevance of our basic research
discoveries to future pain treatments. Here, we will ask how enterochromaffin (EC) cells transmit noxious signals
from the gut lumen to the spinal cord. EC cells are key sensory cells in the intestinal epithelium that release
serotonin onto primary sensory nerve fibers, thereby evoking a sensation of discomfort and pain in response to
luminal irritants, such as bacterial metabolites, inflammatory agents, or ingested chemicals. The goals of this
collaborative effort are to use activating and silencing approaches to examine functional connections between
EC cells and sensory nerve fibers. We will couple these methods with transcriptome profiling, viral tracing, and
electrophysiological methods to gain insights into the molecular and functional identity of these fibers. Another
key goal is to determine whether EC cell signaling pathways exhibit sex-specific differences, an important
question that may relate to the higher prevalence of GI visceral pain syndromes experienced by women.
 Our team brings an unusually wide ranging and innovative approach to this area of pain research that
includes expertise in the neurophysiology, pharmacology, and anatomy of nociceptive and pain circuits, visceral
tissue anatomy and development, and relevant clinical experience. This knowledge base is supported by
complementary technological approaches that will enable us to connect molecular and mechanistic insights to
physiology, visceral nociception, and disease.
 Our focus on the epithelial-nociceptor connectome highlights EC and other enteroendocrine cell types as
potentially powerful control points for neuromodulation of visceral discomfort and pain. A comprehensive
functional, pharmacological, genetic and anatomical characterization of EC-primary afferent-spinal circuits is an
essential first step toward achieving this important goal. As such, our research program fits squarely within the
SPARC mandate to transform our understanding of peripheral nerve-organ interactions and advance strategies
for controlling organ system function.

## Key facts

- **NIH application ID:** 10023951
- **Project number:** 5U01NS113869-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** HOLLY A. INGRAHAM
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $795,511
- **Award type:** 5
- **Project period:** 2019-09-23 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023951

## Citation

> US National Institutes of Health, RePORTER application 10023951, Mapping gut-spinal cord connections in visceral pain (5U01NS113869-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10023951. Licensed CC0.

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