Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals

Background/Aims When a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress-induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects. Methods Twenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated. Results When compared to the baseline IPT value (16.9 ± 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 ± 4.2, 13.1 ± 5.0, 12.1 ± 5.7, 14.0 ± 5.8 minutes, P < 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 ± 17.7, P < 0.01), and cortisol levels at 30 minutes (22.0 ± 6.7 minutes, P < 0.01) and 60 minutes (20.3 ± 6.7 minutes, P < 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values. Conclusion Intravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity.

[1]  N. Rommel,et al.  The effect of intravenous corticotropin-releasing hormone administration on esophageal sensitivity and motility in health. , 2017, American journal of physiology. Gastrointestinal and liver physiology.

[2]  G. Aston-Jones,et al.  Impact of gender on corticotropin‐releasing factor and noradrenergic sensitivity in cocaine use disorder , 2017, Journal of neuroscience research.

[3]  T. Okumura,et al.  Corticotropin-releasing factor receptor type 1 and type 2 interaction in irritable bowel syndrome , 2015, Journal of Gastroenterology.

[4]  Y. Taché,et al.  Role of Corticotropin-releasing Factor Signaling in Stress-related Alterations of Colonic Motility and Hyperalgesia , 2015, Journal of neurogastroenterology and motility.

[5]  Y. Lee,et al.  Irritable bowel syndrome: emerging paradigm in pathophysiology. , 2014, World journal of gastroenterology.

[6]  K. Takakusaki,et al.  Peripheral corticotropin‐releasing factor (CRF) induces stimulation of gastric contractions in freely moving conscious rats: role of CRF receptor types 1 and 2 , 2013, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[7]  N. Seki,et al.  Inhibitory effect of ramosetron on corticotropin releasing factor‐ and soybean oil‐induced delays in gastric emptying in rats , 2012, Journal of gastroenterology and hepatology.

[8]  D. Buffalari,et al.  Corticotrophin releasing factor (CRF) induced reinstatement of cocaine seeking in male and female rats , 2012, Physiology & Behavior.

[9]  M. Hongo,et al.  Visceral hypersensitivity in irritable bowel syndrome , 2011, Journal of gastroenterology and hepatology.

[10]  Young Ju Cho,et al.  Role of Corticotrophin-releasing Factor in the Stress-induced Dilation of Esophageal Intercellular Spaces , 2011, Journal of Korean medical science.

[11]  T. Tomita,et al.  Esophageal Sensation and Esophageal Hypersensitivity - Overview From Bench to Bedside , 2010, Journal of neurogastroenterology and motility.

[12]  I. Liberzon,et al.  Cognitive modulation of endocrine responses to CRH stimulation in healthy subjects , 2010, Psychoneuroendocrinology.

[13]  J. Vandenberghe,et al.  Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatisation? , 2008, Gut.

[14]  P. Anand,et al.  Peripheral and central mechanisms of visceral sensitization in man , 2007, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[15]  T. Nozu,et al.  Corticotropin-releasing factor induces rectal hypersensitivity after repetitive painful rectal distention in healthy humans , 2006, Journal of Gastroenterology.

[16]  P. Dupont,et al.  Influence of experimentally induced anxiety on gastric sensorimotor function in humans. , 2005, Gastroenterology.

[17]  Vikram Bhatia,et al.  Stress and the gastrointestinal tract , 2005, Journal of gastroenterology and hepatology.

[18]  R. Fass Sensory testing of the esophagus. , 2004, Journal of clinical gastroenterology.

[19]  O. Kawamura,et al.  Development and evaluation of FSSG: frequency scale for the symptoms of GERD , 2004, Journal of Gastroenterology.

[20]  M. Hongo,et al.  Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome , 2004, Gut.

[21]  T. Ohkusa,et al.  Oesophageal hypersensitivity in Japanese patients with non‐erosive gastro‐oesophageal reflux diseases , 2004, Alimentary pharmacology & therapeutics.

[22]  H. Mertz Visceral hypersensitivity , 2003, Alimentary pharmacology & therapeutics.

[23]  E. Mayer,et al.  The neurobiology of stress and gastrointestinal disease , 2000, Gut.

[24]  A. Hobson,et al.  Contribution of central sensitisation to the development of noncardiac chest pain , 2000, The Lancet.

[25]  B. Naliboff,et al.  Differential effect of long-term esophageal acid exposure on mechanosensitivity and chemosensitivity in humans. , 1998, Gastroenterology.

[26]  M. Hongo,et al.  Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome , 1998, Gut.

[27]  D. Thompson,et al.  Brain-gut axis in health and disease. , 1998, Gastroenterology.

[28]  Y. Taché,et al.  Central injection of a new corticotropin-releasing factor (CRF) antagonist, astressin, blocks CRF- and stress-related alterations of gastric and colonic motor function. , 1997, The Journal of pharmacology and experimental therapeutics.

[29]  G. Koob,et al.  The Role of CRF in Behavioral Aspects of Stress , 1995, Annals of the New York Academy of Sciences.

[30]  R. Heading,et al.  Lowered oesophageal sensory thresholds in patients with symptomatic but not excess gastro-oesophageal reflux: evidence for a spectrum of visceral sensitivity in GORD. , 1995, Gut.