Veterans Research and Education Foundation, Veterans Affairs Medical Center, Oklahoma City, Oklahoma.
Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Am J Physiol Gastrointest Liver Physiol. 2019 Nov 1;317(5):G609-G617. doi: 10.1152/ajpgi.00150.2018. Epub 2019 Aug 14.
Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, its effects are limited, and mechanisms are largely unknown. We investigated the effects and mechanism of SNS with appropriate parameters on constipation in rats treated with loperamide. First, using rectal compliance as an outcome measure, an experiment was performed to derive effective SNS parameters. Then, a 7-day SNS was performed in rats with constipation induced by loperamide. Autonomic functions were assessed by spectral analysis of heart rate variability (HRV) derived from an electrocardiogram. Serum levels of pancreatic polypeptide (PP), norepinephrine (NE), and acetylcholine (ACh) in colon were assessed. ) Acute SNS at 5 Hz, 100 µs was found effective in enhancing rectal compliance and accelerating distal colon transit ( < 0.05 vs. sham SNS). ) The 7-day SNS normalized loperamide-induced constipation, assessed by the number, weight, and water content of fecal pellets, and accelerated the distal colon transit (29.4 ± 3.7 min with sham SNS vs. 16.4 ± 5.3 min with SNS but not gastric emptying or intestinal transit. ) SNS significantly increased vagal activity ( = 0.035) and decreased sympathetic activity ( = 0.012), assessed by spectral analysis of HRV as well as by the serum PP. ) SNS increased ACh in the colon tissue; atropine blocked the accelerative effect of SNS on distal colon transit. We concluded that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility, mediated via the autonomic-cholinergic function. Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, effects are limited, and mechanisms are largely unknown. This paper shows that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility mediated via the autonomic-cholinergic function.
尽管骶神经刺激 (SNS) 已被用于治疗便秘，但它的参数是从治疗粪便失禁的 SNS 中采用的，效果有限，其机制在很大程度上尚不清楚。我们研究了采用适当参数的 SNS 对洛哌丁胺诱导的便秘大鼠的作用及其机制。首先，我们使用直肠顺应性作为结局指标进行实验，以得出有效的 SNS 参数。然后，对洛哌丁胺诱导的便秘大鼠进行为期 7 天的 SNS 治疗。自主神经功能通过心电图心搏间距变异性 (HRV) 的频谱分析来评估。评估血清中胰多肽 (PP)、去甲肾上腺素 (NE) 和乙酰胆碱 (ACh) 的水平。结果显示，急性 SNS（5 Hz，100 μs）可有效增强直肠顺应性并加速远端结肠通过（<0.05 与假 SNS 比较）。7 天的 SNS 可使洛哌丁胺诱导的便秘正常化，通过粪便颗粒的数量、重量和含水量来评估（假 SNS 组为 29.4±3.7 分钟，SNS 组为 16.4±5.3 分钟，但不影响胃排空或肠通过）。SNS 显著增加了迷走神经活动（=0.035）并降低了交感神经活动（=0.012），通过 HRV 的频谱分析以及血清 PP 来评估。SNS 增加了结肠组织中的 ACh；阿托品可阻断 SNS 对远端结肠通过的加速作用。我们得出结论，采用适当参数的 SNS 通过加速远端结肠蠕动来改善洛哌丁胺诱导的便秘，该作用是通过自主胆碱能功能介导的。尽管骶神经刺激 (SNS) 已被用于治疗便秘，但它的参数是从治疗粪便失禁的 SNS 中采用的，效果有限，其机制在很大程度上尚不清楚。本文表明，采用适当参数的 SNS 通过加速远端结肠蠕动来改善洛哌丁胺诱导的便秘，该作用是通过自主胆碱能功能介导的。
