# Structural and functional mapping of visceral pain afferent neurocircuitries of the colorectum and bladder in preclinical models

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $693,009

## Abstract

ABSTRACT
Irritable Bowel Syndrome (IBS) and interstitial cystitis/painful bladder syndrome (IC/PBS) are common chronic
visceral pain disorders that affect the colon and bladder respectively. Both conditions pose significant health
and financial burden. Notably, IBS and IC/PBS present with considerable overlapping symptoms, whilst
individual patients can suffer from both disorders concurrently. The colon and bladder cross-sensitize and
share spinal innervations. However, despite increased understanding of their symptomatology and the role of
pain afferents in their pathophysiology, there are no effective therapies. The few pharmacological drugs
including opioids have significant adverse effects. Current barriers to the development of effective therapies
for IBS and IC/PBS include: a) Inadequate structural and functional knowledge on the dichotomizing dorsal
root ganglia (DRG) neurons of the distal colon and bladder. b) The lack of adequate investigation on sex
differences in cross-organ sensitization, despite the prevalence of both conditions being higher in women than
in men (female to male ratio: 2:1 for IBS, 5-10:1 for IC/PBS) c) Lack of knowledge of the sensory afferent
innervation and cross-organ sensitization in species with higher translational relevance to humans. We
propose to address these gaps through concurrent monitoring of the colon and bladder pain circuitries in two
pre-clinical models and under 3 specific aims. 1): Structural mapping of colon and bladder pain afferent
neurocircuits: Dichotomizing and non-dichotomizing neurons, their spatial distribution and connectivity. 2):
Functional characterization of colon and bladder afferents in acute and chronic models of cross-organ
sensitization and 3): Map spinal sites of colon and bladder pain and cross-organ sensitization through
neuromodulation. We will use acute and chronic cross-organ sensitization models, state-of-the-art high-
resolution imaging, 3D mapping, dual retrograde tracing of bladder and colon sensory neurons, CLARITY, ex
vivo DRG Ca2+ imaging of dichotomizing neurons, ex vivo electrophysiological recordings from bladder and
colon afferents and transcutaneous spinal stimulation (TSCS) approaches. The murine model will unravel the
classes of pain afferents/neurons and their functional circuits in bowel-to-bladder and bladder-to-bowel acute
and chronic pain cross sensitization. The porcine studies will provide novel information on the structural map
of the colon and bladder dichotomizing neurons and their connections as well as cross sensitization of pain
responses. It will also allow us to gain insight on the use of TSCS to map spinal cord circuits and backtrack
colon and bladder pain circuits and its translational feasibility for human use. The combined multidisciplinary
approaches will fill the gaps in current knowledge on the colon/bladder dichotomizing DRG neurons, spatial
distribution and connections as well as the plasticity in the pain circuitries post sensitizatio...

## Key facts

- **NIH application ID:** 10021471
- **Project number:** 5U01NS113871-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** MILLION MULUGETA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $693,009
- **Award type:** 5
- **Project period:** 2019-09-19 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021471

## Citation

> US National Institutes of Health, RePORTER application 10021471, Structural and functional mapping of visceral pain afferent neurocircuitries of the colorectum and bladder in preclinical models (5U01NS113871-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10021471. Licensed CC0.

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