# Regulation of swallow and the effects of high cervical spinal cord injury

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2021 · $336,875

## Abstract

ABSTRACT. Swallow is a basic, critical behavior necessary for the movement of liquids and food from the
mouth, through the esophagus to the stomach. When swallow is abnormal (dysphagia), liquid and food may
enter the larynx and trachea (aspiration) causing subsequent pneumonia. While the collective literature reports
a large variance in the incidence of dysphagia, a 2017 prospective study shows disordered swallow production
in 76% of cSCI patients. Our long-term goal is to understand the mechanism(s) of dysphagia following cSCI,
and to develop novel therapies which have a high likelihood of clinical utility. Our central hypothesis is that
spinal circuits are critical for the successful execution of swallow. Specifically, the central pattern generator
(CPG) in the brainstem controlling this vital airway protective behavior is connected to circuitry in the cervical
spinal cord. Our preliminary data demonstrates that acute C2 and C3 hemisections depress diaphragm activity
which results in positive intra-thoracic pressure during swallow. These lesions also increased upper airway
muscle recruitment considerably (~200-800%), with a total loss of sequential muscle recruitment during the
pharyngeal phase of swallow. Additionally, a high dose of a 5-HT1A agonist increased diaphragm activity during
swallow, which was accompanied by restoration of upper airway sequential activation. Guided by strong
preliminary data our central hypothesis will be tested with the following aims: Aim 1: Identify the effects of
cervical spinal cord disruption on the swallow motor pattern; and Aim 2: Determine the therapeutic efficacy of
8-OH-DPAT (5-HT1A agonist) on recovery of swallow function after acute spinal hemisection. We will use
electrophysiology techniques to determine the effects of C2, C3 and C4 hemisection on execution of swallow.
We will also determine changes in swallow function with a combined protocol of C2 hemisection and medial
myelotomy. The therapeutic effectiveness of 8-OH-DPAT on swallow function will be tested in intact animals as
well as with C2, C3 and C4 hemisections. To ensure the treatment effects are related to 5-HT1A receptor
activation, a series of experiments will also be performed with the 5-HT1A antagonist WAY-100635. These
studies will be the first to show, in an animal model, that loss of cervical spinal pathways has a deleterious
effect on swallow. Additionally, we will provide pre-clinical evidence that a 5-HT1A receptor agonist can be used
to treat swallow impairments, which will be the first of its kind for dysphagia. This information will educate the
clinical community about risk of dysphagia after cSCI and provide options for novel interventions.

## Key facts

- **NIH application ID:** 10063070
- **Project number:** 5R01NS110169-03
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Teresa G Pitts
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $336,875
- **Award type:** 5
- **Project period:** 2018-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063070

## Citation

> US National Institutes of Health, RePORTER application 10063070, Regulation of swallow and the effects of high cervical spinal cord injury (5R01NS110169-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10063070. Licensed CC0.

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