Swallowing dysfunction following radiation to the rat mylohyoid muscle is associated with sensory neuron injury

Abstract

Radiation based treatments for oropharyngeal and hypopharyngeal cancers result in impairments in swallowing mobility, but the mechanisms behind the dysfunction are not clear. The purpose of this study was to determine if we could establish an animal model of radiation-induced dysphagia in which mechanisms could be examined. We hypothesized that (1) radiation focused at the depth of the mylohyoid muscle would alter normal bolus transport and bolus size; and (2) that radiation to the mylohyoid muscle will induce an injury/stress-like response in trigeminal sensory neurons whose input might modulate swallow. Rats were exposed to 48 or 56 Gy of radiation to the mylohyoid given 8 Gy in 6 or 7 fractions. Swallowing function was evaluated by videofluoroscopy 2- and 4-weeks following treatment. Neuronal injury/stress was analyzed in trigeminal ganglion by assessing ATF3 and GAP-43 mRNA at 2-, 4- and 8-weeks post. Irradiated rats exhibited decreases in bolus movement through the pharynx and alterations in bolus clearance. Additionally, ATF3 and GAP-43 mRNAs were upregulated in trigeminal ganglion in irradiated rats, suggesting that radiation to mylohyoid muscle induced an injury/stress response in neurons with cell bodies that are remote from the irradiated tissue. These results suggest that radiation-induced dysphagia can be assessed in the rat, and that radiation induces injury/stress-like responses in sensory neurons.