The effect of intravenous corticotropin-releasing hormone administration on esophageal sensitivity and motility in health.
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:P= 0.0023; PTT:P= 0.0253). CRH had no influence on the other stimulations. DCI was increased for all boluses (liquid,P= 0.0012; semisolid,P= 0.0017; solid,P= 0.0107). Impedance ratio for liquid (P< 0.0001) and semisolid swallows (P= 0.0327) decreased after CRH. IBP slope increased after CRH for semisolid (P= 0.0041) and solid (P= 0.0003) swallows. PFI increased for semisolid (P= 0.0017) and solid swallows (P= 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.NEW & NOTEWORTHYThis 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.
Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Belgium.
Charlotte
C
Broers
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.|Physiology and Gastroenterology Department, Rouen University Hospital, France.
Chloé
C
Melchior
Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Belgium.
Lukas
L
Van Oudenhove
Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Belgium.|Department of Gastroenterology, Leuven University Hospitals, Leuven, Belgium.
Tim
T
Vanuytsel
Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Belgium.
Brecht
B
Van Houtte
Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Belgium.|Experimental Oto-Rhino-Laryngology, Department of Neurosciences, KU Leuven, Belgium.
Charlotte
C
Scheerens
Experimental Oto-Rhino-Laryngology, Department of Neurosciences, KU Leuven, Belgium.
Nathalie
N
Rommel
Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Belgium; jan.tack@med.kuleuven.ac.be.|Department of Gastroenterology, Leuven University Hospitals, Leuven, Belgium.
Jan
J
Tack
Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Belgium.
Ans
A
Pauwels
D000293:Adolescent; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D003679:Deglutition / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010528:Peristalsis / Q000187:drug effects / Q000502:physiology*; D011312:Pressure; D055815:Young Adult
D003346:Corticotropin-Releasing Hormone
corticotropin-releasing hormone; esophageal motility; esophageal sensitivity; gastroesophageal reflux disease; stress