# Mechanisms underlying radiation-induced dysphagia

> **NIH NIH R21** · UNIVERSITY OF LOUISVILLE · 2022 · $219,491

## Abstract

ABSTRACT
 Radiation-induced dysphagia is a devastating complication of chemoradiation treatment for head and neck
cancer. Deficits in oral and pharyngeal movement during swallowing are the most prevalent cause of radiation-
induced dysphagia. The adverse effects of these swallowing problems can lead to long-term dietary
restrictions, malnutrition, and placement of a feeding tube to prevent aspiration. Recent evidence in other
areas of the body demonstrate that radiation can damage peripheral nerves resulting in changes in motor
function. However, the neural mechanisms underlying radiation-induced dysphagia are unknown. An
understanding of the pathophysiology of radiation-induced dysphagia is needed to develop more effective
therapeutic targets aimed at preserving post chemoradiation swallowing function. Swallowing is a coordinated
activity controlled by a neural pattern-generating circuitry in the brainstem that relies heavily on sensory
information. Nociceptors are a subset of sensory neurons that are sensitized by tissue injury. When nociceptor
sensory axons are damaged, they trigger protective responses that can drive changes in neural control leading
to disturbances in coordinated motor output. We propose that nociceptor activity interfering with swallowing
function may be another potential mechanism at play after chemoradiation muscle injury. In the proposed
study, we will characterize how oropharyngeal swallowing is affected by chemoradiation and determine
whether injury of sensory neurons can contribute to dysphagia post-treatment. We hypothesize that
chemoradiation-induced axon injury is associated with changes in oral and pharyngeal swallowing kinematics
after treatment. This research has two specific aims that are strongly supported by preliminary data. In Aim 1
we will determine the effect of chemoradiation to the mylohyoid muscle on the movement of the oral and
pharyngeal structures during swallowing. Kinematic analysis and force measures will be used to quantify
functional deficits. In Aim 2 we will determine the nerve injury/stress-like response induced in trigeminal
sensory neurons following chemoradiation to the mylohyoid muscle. We will identify sensory neurons in the
trigeminal ganglion projecting from the mylohyoid and measure their expression of injury/stress-induced
markers. We will also test alternative mechanisms and develop a predictive model to quantify the complication
risk of treatment to tissue and behavioral outcomes. The proposed experiments will establish the feasibility of a
novel neural-based mechanism underlying radiation-induced dysphagia and define specific points of
swallowing dysfunction after chemoradiation in the rat that will serve as targets for assessing future treatments.

## Key facts

- **NIH application ID:** 10512548
- **Project number:** 1R21CA263107-01A1
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Suzanne N. King
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $219,491
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512548

## Citation

> US National Institutes of Health, RePORTER application 10512548, Mechanisms underlying radiation-induced dysphagia (1R21CA263107-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10512548. Licensed CC0.

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