Gastrointestinal Physiology Laboratory, Hospital de Mataró, Consorci Sanitari del Maresme, 08304 Mataró, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, 28029 Barcelona, Spain.
Int J Mol Sci. 2022 Sep 15;23(18):10773. doi: 10.3390/ijms231810773.
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.
流体增稠是与衰老或神经疾病相关的口咽吞咽障碍（OD）患者的主要代偿策略，但目前仍没有药物治疗方法。我们旨在比较通过增加射流粘度与使用 TRPV1、TRPA1 或 TRPM8 激动剂进行急性刺激对 OD 患者吞咽反应的生物力学和神经生理学的影响。我们回顾性分析了来自我们实验室的七项针对 329 例 OD 患者的研究。通过视频透视和咽感觉诱发电位（pSEP）比较了将剪切粘度增加到 3682 mPa·s 的效果与向射流中添加以下物质的效果：辣椒素（TRPV1，150 μM/10 μM）、胡椒碱（TRPA1/V1，1 mM/150 μM）、薄荷醇（TRPM8，1 mM/10 mM）、肉桂醛-锌（TRPA1，100 ppm−70 mM）、柠檬醛（TRPA1，250 ppm）或柠檬醛-异胡薄荷醇（TRPA1-TRPM8，250 ppm−200 ppm）。通过将射流速度延迟 20.7±7.0%和将声门裂闭合时间延迟 23.1±3.7%，流体增稠将吞咽安全性提高了 80%（p<0.0001）。辣椒素 150μM 或胡椒碱 1 mM 可将吞咽安全性分别提高 50%（p<0.01）和 57.1%（p<0.01），将声门裂闭合时间分别缩短 27.6%（p<0.001）和 19.5%（p<0.01），射流速度分别提高 24.8%（p<0.01）和 16.9%（p<0.05）。肉桂醛-锌可使 pSEP 的 P2 潜伏期缩短 11.0%（p<0.01），并使 N2-P2 幅度降低 35%（p<0.01）。综上所述，TRPV1 和 TRPV1/A1 激动剂是开发新的药物治疗策略以促进慢性 OD 患者的大脑和吞咽功能恢复的最佳候选物。
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