Broers Charlotte, Melchior Chloé, Van Oudenhove Lukas, Vanuytsel Tim, Van Houtte Brecht, Scheerens Charlotte, Rommel Nathalie, Tack Jan, Pauwels Ans
Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Belgium.
Institut National de la Santé et de la Recherche Médicale, UMR 1073, Institute for Research and Innovation in Biomedicine, Normandy University, Rouen, France; and.
Am J Physiol Gastrointest Liver Physiol. 2017 May 1;312(5):G526-G534. doi: 10.1152/ajpgi.00437.2016. Epub 2017 Mar 23.
Esophageal hypersensitivity is important in gastroesophageal reflux disease (GERD) patients who are refractory to acid-suppressive therapy. Stress affects visceral sensitivity and exacerbates heartburn in GERD. Peripheral CRH is a key mediator of the gut stress response. We hypothesize that CRH increases esophageal sensitivity and alters esophageal motility in health. Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 14 healthy subjects after administration of placebo or CRH (100 μg iv). Perception scores were assessed for first perception, pain perception threshold (PPT), and pain tolerance threshold (PTT). Esophageal motility was investigated by high-resolution impedance manometry, before and after CRH and evaluated by distal contractile integral (DCI) and intrabolus pressure (IBP). Pressure flow analysis assessed bolus clearance (impedance ratio), degree of pressurization needed to propel bolus onward (IBP slope), and pressure flow (pressure flow index, PFI). Stress and mood were assessed during the study. Sensitivity to mechanical distention was increased after CRH compared with placebo (PPT: = 0.0023; PTT: = 0.0253). CRH had no influence on the other stimulations. DCI was increased for all boluses (liquid, = 0.0012; semisolid, = 0.0017; solid, = 0.0107). Impedance ratio for liquid ( < 0.0001) and semisolid swallows ( = 0.0327) decreased after CRH. IBP slope increased after CRH for semisolid ( = 0.0041) and solid ( = 0.0003) swallows. PFI increased for semisolid ( = 0.0017) and solid swallows ( = 0.0031). CRH increased esophageal sensitivity to mechanical distention, not to the other stimulation modalities. CRH increased esophageal contractility and tone, decreased LES relaxation, increased esophageal bolus pressurization, improved esophageal bolus clearance, and increased pressure flow. This is the first study to address the effect of corticotropin-releasing hormone (CRH) on esophageal sensitivity and alterations in motility in health. CRH administration increased esophageal sensitivity to mechanical distention. This effect is accompanied by an increase in esophageal contractility and tone and a decrease in lower esophageal sphincter relaxation. CRH increased esophageal bolus pressurization, improved esophageal bolus clearance, and increased pressure flow. The changes in esophageal contractile properties may underlie the increased sensitivity to mechanical distention after CRH.
食管超敏反应在对抑酸治疗无效的胃食管反流病（GERD）患者中具有重要意义。压力会影响内脏敏感性并加重GERD患者的烧心症状。外周促肾上腺皮质激素释放激素（CRH）是肠道应激反应的关键介质。我们假设CRH会增加健康状态下的食管敏感性并改变食管动力。在14名健康受试者中，在给予安慰剂或CRH（静脉注射100μg）后，评估食管对热、机械、电和化学刺激的敏感性。评估首次感知、疼痛感知阈值（PPT）和疼痛耐受阈值（PTT）的感知评分。在给予CRH前后，通过高分辨率阻抗测压法研究食管动力，并通过远端收缩积分（DCI）和团注内压力（IBP）进行评估。压力流分析评估团注清除率（阻抗比）、推动团注前进所需的增压程度（IBP斜率）和压力流（压力流指数，PFI）。在研究过程中评估压力和情绪。与安慰剂相比，CRH给药后对机械扩张的敏感性增加（PPT： = 0.0023；PTT： = 0.0253）。CRH对其他刺激无影响。所有团注（液体， = 0.0012；半固体， = 0.0017；固体， = 0.0107）的DCI均增加。CRH给药后，液体（ < 0.0001）和半固体吞咽的阻抗比（ = 0.0327）降低。CRH给药后半固体（ = 0.0041）和固体（ = 0.0003）吞咽的IBP斜率增加。半固体（ = 0.0017）和固体吞咽的PFI增加。CRH增加食管对机械扩张的敏感性，而对其他刺激方式无影响。CRH增加食管收缩性和张力，降低下食管括约肌松弛，增加食管团注增压，改善食管团注清除，并增加压力流。这是第一项研究促肾上腺皮质激素释放激素（CRH）对健康状态下食管敏感性和动力改变影响的研究。CRH给药增加食管对机械扩张的敏感性。这种效应伴随着食管收缩性和张力的增加以及下食管括约肌松弛的降低。CRH增加食管团注增压，改善食管团注清除，并增加压力流。食管收缩特性的改变可能是CRH给药后对机械扩张敏感性增加的基础。
