# Spinal dopaminergic mechanisms regulating the micturition reflex after spinal cord injury

> **NIH NIH R01** · DREXEL UNIVERSITY · 2021 · $372,470

## Abstract

Project summary
Dopamine (DA) neurons in the mammalian central nervous system (CNS) are thought to be restricted
to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction
between midbrain DA neurons and the pontine micturition center. However, we have recently
characterized that DA is produced in the rat spinal cord and modulates the bladder reflex. Traumatic
spinal cord injury (SCI) interrupts spinobulbospinal micturition pathways and eliminates voluntary
voiding. Although a spinal micturition reflex is established over time and induces partial recovery of
urination, the incidence of bladder hyperactivity and detrusor-sphincter dyssynergia (DSD) causes
inefficient emptying and incontinence, which is detrimental to the health of SCI patients. We
hypothesize that there are endogenous spinal DA-ergic mechanisms regulating the micturition reflex,
and pharmacological manipulation of these mechanisms will improve lower urinary tract (LUT) function
following SCI. In our preliminary data, we have observed numerous tyrosine hydroxylase (TH)+ neurons
in the autonomic nuclei and the superficial dorsal horn of rat lumbosacral spinal cord. Following a
complete thoracic SCI to remove supraspinal control, remarkably more TH+ neurons emerged in the
lower cord, which coincides with a local sustained, low level of DA expression. Furthermore,
suppression of spinal DA signaling reduces bladder activity whereas activation of these pathways
increases bursting duration of the external urethral sphincter (EUS). Accordingly, this proposed project
will not only comprehensively address some fundamental questions but also test a novel therapeutic
strategy to treat LUT dysfunction after SCI. In aim 1, we will determine whether TH+ cells in rat lower
spinal cord undergo plasticity following SCI and are involved in the spinal micturition reflex circuits. In
aim 2, we will elucidate whether these TH+ neurons exert DA-ergic regulation of the micturition reflex
after SCI. In aim 3, we will identify whether pharmacological stimulation of spinal DA-ergic pathways
improves urinary functional recovery in rats with SCI. The results of this project will uncover the spinal
DA-ergic system and elucidate its role in the micturition. We anticipate developing an innovative
approach to enhance urinary efficiency and continence, thereby improving quality of life in patients with
SCI.

## Key facts

- **NIH application ID:** 10075323
- **Project number:** 5R01NS099076-05
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Shaoping Hou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $372,470
- **Award type:** 5
- **Project period:** 2016-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075323

## Citation

> US National Institutes of Health, RePORTER application 10075323, Spinal dopaminergic mechanisms regulating the micturition reflex after spinal cord injury (5R01NS099076-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10075323. Licensed CC0.

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