Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Division of Neuroimmunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Neuromodulation. 2024 Feb;27(2):284-294. doi: 10.1016/j.neurom.2023.04.001. Epub 2023 May 15.
OBJECTIVES: The aims of this study were to investigate analgesic effects of vagus nerve stimulation (VNS) on visceral hypersensitivity (VH) in a rodent model of functional dyspepsia (FD) and to compare invasive VNS with noninvasive auricular VNS (aVNS). MATERIALS AND METHODS: Eighteen ten-day-old male rats were gavaged with 0.1% iodoacetamide (IA) or 2% sucrose solution for six days. After eight weeks, IA-treated rats were implanted with electrodes for VNS or aVNS (n = 6 per group). Different parameters, varying in frequency and stimulation duty cycle, were tested to find the best parameter based on the improvement of VH assessed by electromyogram (EMG) during gastric distension. RESULTS: Compared with sucrose-treated rats, visceral sensitivity was increased significantly in IA-treated "FD" rats and ameliorated remarkably by VNS (at 40, 60, and 80 mm Hg; p ≤ 0.02, respectively) and aVNS (at 60 and 80 mm Hg; p ≤ 0.05, respectively) with the parameter of 100 Hz and 20% duty cycle. There was no significant difference in area under the curve of EMG responses between VNS and aVNS (at 60 and 80 mm Hg, both p > 0.05). Spectral analysis of heart rate variability revealed a significant enhancement in vagal efferent activity while applying VNS/aVNS compared with sham stimulation (p < 0.01). In the presence of atropine, no significant differences were noted in EMG after VNS/aVNS. Naloxone blocked the analgesic effects of VNS/aVNS. CONCLUSIONS: VNS/aVNS with optimized parameter elicits ameliorative effects on VH, mediated by autonomic and opioid mechanisms. aVNS is as effective as direct VNS and has great potential for treating visceral pain in patients with FD.
目的：本研究旨在探讨迷走神经刺激（VNS）对功能性消化不良（FD）大鼠内脏高敏性（VH）的镇痛作用，并比较有创性 VNS 与非侵入性耳甲迷走神经刺激（aVNS）。
材料和方法：将 18 只 10 日龄雄性大鼠灌胃 0.1%碘乙酰胺（IA）或 2%蔗糖溶液 6 天。8 周后，IA 处理大鼠植入电极进行 VNS 或 aVNS（每组 n=6）。测试不同频率和刺激占空比的参数，根据胃扩张时肌电图（EMG）评估的 VH 改善情况找到最佳参数。
结果：与蔗糖处理大鼠相比，IA 处理的“FD”大鼠内脏敏感性显著增加，VNS（在 40、60 和 80 mm Hg 时；p≤0.02，分别）和 aVNS（在 60 和 80 mm Hg 时；p≤0.05，分别）显著改善，参数为 100 Hz 和 20%占空比。VNS 和 aVNS 之间在 60 和 80 mm Hg 时 EMG 反应的曲线下面积没有显著差异（均 p>0.05）。心率变异性的频谱分析显示，与假刺激相比，应用 VNS/aVNS 时迷走神经传出活动显著增强（p<0.01）。在给予阿托品的情况下，VNS/aVNS 后 EMG 无显著差异。纳洛酮阻断了 VNS/aVNS 的镇痛作用。
结论：优化参数的 VNS/aVNS 对 VH 具有改善作用，这种作用通过自主和阿片样物质机制介导。aVNS 与直接 VNS 一样有效，对治疗 FD 患者的内脏疼痛具有很大的潜力。
Am J Physiol Gastrointest Liver Physiol. 2021-5-1
J Transl Gastroenterol. 2025-6
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