# Determining the topology and molecular profiles of nociceptive DRG neurons innervating distal colon and rectum

> **NIH NIH U01** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $669,580

## Abstract

Project Summary/Abstract
 Chronic visceral pain is the cardinal symptom of patients with irritable bowel syndrome (IBS) affecting up to
15% of the U.S. population. Efficacious and reliable therapeutic intervention is still unavailable despite the
tremendous economic burden imposed by visceral pain. Pharmacological treatments of visceral pain in IBS are
largely unsatisfactory with side effects outweighing therapeutic benefits. In contrast, neuromodulation (e.g.,
spinal cord stimulation) as an alternative to drugs has much fewer side effects.
 Recent advances in neuromodulation of the dorsal root ganglions (DRG) relieves certain somatic and
neuropathic pain. Hence, the DRG appears to be a promising target for next-generation neuromodulatory
devices to treat IBS-related visceral pain. However, knowledge is missing regarding the topological distribution
and molecular profiles of functionally-characterized DRG neurons innervating the colon and rectum (colorectum),
especially colorectal nociceptors. This has significantly hindered the further development of DRG
neuromodulation that selectively affects a subset of DRG neurons in treating visceral pain in IBS. We aim to
leverage our recent technical advances in optical electrophysiology via Ca2+ imaging and single-cell
transcriptome assay of sensory neurons to characterize the topology and molecular profiles of colorectal
nociceptors in the thoracolumbar and lumbosacral DRG.
 Three specific aims are proposed. Specific Aim 1 will quantify the topological distribution of mechano-
nociceptors of the colorectum in the thoracolumbar and lumbosacral DRG in control and prolonged colorectal
hypersensitivity. Specific Aim 2 will quantify the topological distribution of silent nociceptors of the colorectum in
the thoracolumbar and lumbosacral DRG in control and prolonged colorectal hypersensitivity. Specific Aim 3 will
define the molecular profiles of mechano- and silent nociceptors of the colorectum in the thoracolumbar and
lumbosacral DRG in control and prolonged colorectal hypersensitivity. By establishing a high-throughput optical
electrophysiology method, we will be able to functionally characterize a large number (>2000) of colorectal DRG
neurons (including nociceptors) and reveal their topological distributions in thoracolumbar and lumbosacral DRG.
The single-cell transcriptome analysis on colorectal nociceptors will reveal promising targets for chemical
neuromodulation of the DRG. The outcomes of this research will guide the design of next-generation
neuromodulatory devices that target DRG for effective management of chronic visceral pain while minimizing
off-target side effects.

## Key facts

- **NIH application ID:** 10023955
- **Project number:** 5U01NS113873-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Bin Feng
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $669,580
- **Award type:** 5
- **Project period:** 2019-09-24 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023955

## Citation

> US National Institutes of Health, RePORTER application 10023955, Determining the topology and molecular profiles of nociceptive DRG neurons innervating distal colon and rectum (5U01NS113873-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10023955. Licensed CC0.

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