Department of Otolaryngology-Head and Neck Surgery and Communicative Disorders, University of Louisville, Louisville, Kentucky.
Department of Radiation Oncology, University of Louisville, Louisville, Kentucky.
J Appl Physiol (1985). 2021 Apr 1;130(4):1274-1285. doi: 10.1152/japplphysiol.00664.2020. Epub 2021 Feb 18.
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 ) radiation focused at the depth of the mylohyoid muscle would alter normal bolus transport and bolus size and ) 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 64 Gy of radiation to the mylohyoid given 8 Gy in 6 or 8 fractions. Swallowing function was evaluated by videofluoroscopy 2 and 4 wk following treatment. Neuronal injury/stress was analyzed in trigeminal ganglion by assessing activating transcription factor (ATF)3 and GAP-43 mRNAs at 2, 4, and 8 wk post treatment. Irradiated rats exhibited decreases in bolus movement through the pharynx and alterations in bolus clearance. In addition, 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 radiation induces injury/stress-like responses in sensory neurons. Radiation-based treatments for head and neck cancer can cause significant impairments in swallowing mobility. This study provides new evidence supporting the possibility of a neural contribution to the mechanisms of swallowing dysfunction in postradiation dysphagia. Our data demonstrated that radiation to the mylohyoid muscle, which induces functional deficits in swallowing, also provokes an injury/stress-like response in the ganglion, innervating the irradiated muscle.
头颈部放射治疗会导致口咽和下咽癌患者吞咽运动功能障碍，但吞咽功能障碍的机制尚不清楚。本研究旨在建立一种放射诱导吞咽困难的动物模型，以研究其机制。我们假设：（1）聚焦于颏舌肌深度的放射治疗会改变正常的食团转运和食团大小；（2）颏舌肌的放射治疗会引起三叉神经感觉神经元的损伤/应激样反应，其输入可能调节吞咽。大鼠接受 48 或 64Gy 辐射至颏舌肌，6 或 8 次 8Gy 分割。治疗后 2 和 4 周，通过荧光透视法评估吞咽功能。通过评估激活转录因子 3 (ATF3) 和 GAP-43 mRNA 在治疗后 2、4 和 8 周三叉神经节中的神经元损伤/应激，分析三叉神经节中的神经元损伤/应激。接受照射的大鼠表现出食团在咽部运动减少和食团清除改变。此外，在接受照射的大鼠三叉神经节中，ATF3 和 GAP-43 mRNA 上调，表明颏舌肌的放射治疗诱导了远离照射组织的神经元的损伤/应激反应。这些结果表明，在大鼠中可以评估放射诱导的吞咽困难，并且放射诱导感觉神经元的损伤/应激样反应。头颈部癌症的放射治疗会导致显著的吞咽运动功能障碍。本研究为放射后吞咽困难吞咽功能障碍机制中存在神经贡献提供了新的证据。我们的数据表明，颏舌肌的放射治疗，会引起吞咽功能的功能缺陷，也会引起支配受照射肌肉的神经节的损伤/应激样反应。
