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Mechanisms underlying radiation-induced dysphagia

Award Number: R21CA263107
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Mechanisms underlying radiation-induced dysphagia - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$3,888 )
2026	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cancer Treatment Research	000	2	12/9/2025	NON-COMPETING CONTINUATION	-$3,888
														Subtotal = -$3,888

Issue Date FY: 2023 ( Subtotal = $179,252 )
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cancer Treatment Research	000	2	8/1/2023	NON-COMPETING CONTINUATION	$179,252
														Subtotal = $179,252

Issue Date FY: 2022 ( Subtotal = $219,491 )
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cancer Treatment Research	000	1	7/25/2022	NEW	$219,491
														Subtotal = $219,491

Grand Total All Awards = $394,855

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Mechanisms underlying radiation-induced dysphagia

Award Number: R21CA263107

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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