Abstract：
Fluid thickening is the main compensatory strategy for patients with oropharyngeal dysphagia (OD) associated with aging or neurological diseases, and there is still no pharmacological treatment. We aimed to compare the effects of increasing bolus viscosity with that of acute stimulation with TRPV1, TRPA1 or TRPM8 agonists on the biomechanics and neurophysiology of swallow response in patients with OD. We retrospectively analyzed seven studies from our laboratory on 329 patients with OD. The effect of increasing shear viscosity up to 3682 mPa·s was compared by videofluoroscopy and pharyngeal sensory evoked potentials (pSEP) with that of adding to the bolus: capsaicin (TRPV1, 150 μM/10 μM), piperine (TRPA1/V1, 1 mM/150 μM), menthol (TRPM8, 1 mM/10 mM), cinnamaldehyde-zinc (TRPA1, 100 ppm−70 mM), citral (TRPA1, 250 ppm) or citral-isopulegol (TRPA1-TRPM8, 250 ppm−200 ppm). Fluid thickening improved the safety of swallow by 80% (p < 0.0001) by delaying bolus velocity by 20.7 ± 7.0% and time to laryngeal vestibule closure (LVC) by 23.1 ± 3.7%. Capsaicin 150μM or piperine 1 mM significantly improved safety of swallow by 50% (p < 0.01) and 57.1% (p < 0.01) by speeding time to LVC by 27.6% (p < 0.001) and 19.5% (p < 0.01) and bolus velocity by 24.8% (p < 0.01) and 16.9% (p < 0.05), respectively. Cinnamaldehyde-zinc shortened the P2 latency of pSEPs by 11.0% (p < 0.01) and reduced N2-P2 amplitude by 35% (p < 0.01). In conclusion, TRPV1 and TRPV1/A1 agonists are optimal candidates to develop new pharmacological strategies to promote the recovery of brain and swallow function in patients with chronic OD.
摘要：
液体增厚是与衰老或神经系统疾病相关的口咽部吞咽困难（OD）患者的主要代偿策略，仍然没有药物治疗。我们旨在比较增加推注粘度与TRPV1，TRPA1或TRPM8激动剂急性刺激对OD患者吞咽反应的生物力学和神经生理学的影响。我们回顾性分析了实验室对329例OD患者的7项研究。通过视频透视检查和咽部感觉诱发电位（pSEP）比较了将剪切粘度增加到3682mPa·s的效果，并将其添加到推注中：辣椒素（TRPV1，150μM/10μM），胡椒碱（TRPA1/V1，1mM/150μM），薄荷醇（TRPM8，1mM/10mM），肉桂醛锌（TRPA1，100ppm-70mM），柠檬醛(TRPA1,250ppm)或柠檬醛-异胡勒醇(TRPA1-TRPM8,250ppm-200ppm)。液体增稠通过将推注速度延迟20.7±7.0％和将喉前庭闭合时间（LVC）延迟23.1±3.7％，将吞咽的安全性提高了80％（p＆lt;0.0001）。辣椒素150μM或胡椒碱1mM通过将时间加速到LVC27.6%(p<0.001)和19.5%(p<0.01)和推注速度24.8%(p<0.01)和16.9%(p<0.05),显著提高吞咽安全性50%(p<0.01)和57.1%(p<0.01),分别。肉桂醛锌使pSEP的P2潜伏期缩短了11.0％（p＆lt;0.01），使N2-P2振幅降低了35％（p＆lt;0.01）。总之,TRPV1和TRPV1/A1激动剂是开发新的药理学策略以促进慢性OD患者脑和吞咽功能恢复的最佳候选者。
