Division of Dysphagia Rehabilitation, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
Department of Physiology, The Nippon Dental University School of Life Dentistry at Niigata, Chuo-ku, Niigata, Japan.
Am J Physiol Gastrointest Liver Physiol. 2020 Nov 1;319(5):G564-G572. doi: 10.1152/ajpgi.00233.2020. Epub 2020 Sep 2.
Capsaicin powerfully evokes the swallowing reflex and is a known therapeutic agent for improving dysphagia and preventing aspiration pneumonia. However, the role of capsaicin-sensitive nerves in the initiation of swallowing evoked by various natural stimuli remains unclear. To explore this question, we blocked laryngeal capsaicin-sensitive nerves following the coapplication of QX-314 and capsaicin (QX/Cap), and investigated the effects on swallowing evoked by mechanical and chemical stimulation in anesthetized rats. Swallows were evoked by capsaicin, carbonated water (CW), distilled water (DW), and punctate mechanical stimulation using von Frey filaments applied topically to the larynx. Swallows were documented by recording electromyographic activation of the suprahyoid and thyrohyoid muscles. The initiation of swallowing by capsaicin was strongly suppressed at 5 min following QX/Cap treatment and returned in a time-dependent manner. CW-evoked swallows at 5 min following QX/Cap treatment were significantly diminished compared with before and 30 min after treatment. In contrast, DW-evoked and mechanically evoked swallows were unchanged by QX/Cap treatment. Furthermore, CW-evoked swallows were virtually abolished by transection of the superior laryngeal nerves and significantly decreased by the topical application of acid-sensing ion channel-3 (ASIC3) inhibitor APETx2, but they were not affected by the nonselective transient receptor potential channel inhibitor ruthenium red or the ASIC1 inhibitor mambalgin-1. Taken together, we speculate that capsaicin-sensitive nerves play an important role in the initiation of CW-evoked swallows. The initiation of swallowing evoked by laryngeal capsaicin and carbonated water application was diminished by the coapplication of QX-314 and capsaicin. Carbonated water-evoked swallows were also abolished by transection of the superior laryngeal nerves and were inhibited by the acid-sensing ion channel-3 inhibitor. Capsaicin-sensitive nerves are involved in the initiation of carbonated water-evoked swallows.
辣椒素能强烈诱发吞咽反射，是改善吞咽困难和预防吸入性肺炎的已知治疗药物。然而，各种天然刺激物诱发吞咽时，辣椒素敏感神经的作用尚不清楚。为了探讨这个问题，我们在同时应用 QX-314 和辣椒素（QX/Cap）后，阻断了喉内的辣椒素敏感神经，并在麻醉大鼠中研究了机械和化学刺激诱发吞咽的影响。通过向喉部局部应用 von Frey 纤维，用辣椒素、碳酸水（CW）、蒸馏水（DW）和点状机械刺激来诱发吞咽。通过记录舌骨上和舌骨下肌肉的肌电图激活来记录吞咽。在 QX/Cap 处理后 5 分钟，辣椒素诱发的吞咽明显受到抑制，并呈时间依赖性恢复。在 QX/Cap 处理后 5 分钟，CW 诱发的吞咽与处理前和处理后 30 分钟相比明显减少。相比之下，DW 诱发和机械诱发的吞咽不受 QX/Cap 处理的影响。此外，CW 诱发的吞咽几乎被切断上喉神经所消除，并且被酸敏感离子通道-3（ASIC3）抑制剂 APETx2 显著减少，但不受非选择性瞬时受体电位通道抑制剂钌红或 ASIC1 抑制剂 mambalgin-1 的影响。综上所述，我们推测辣椒素敏感神经在 CW 诱发的吞咽开始中起重要作用。应用 QX-314 和辣椒素后，喉内辣椒素和碳酸水应用诱发的吞咽开始减少。碳酸水诱发的吞咽也被切断上喉神经所消除，并被酸敏感离子通道-3 抑制剂所抑制。辣椒素敏感神经参与碳酸水诱发吞咽的开始。
