The effect of intravenous corticotropin-releasing hormone administration on esophageal sensitivity and motility in health

Broers, Charlotte; Melchior, Chloé; Oudenhove, Lukas Van; Vanuytsel, Tim; Houtte, Brecht Van; Scheerens, Charlotte; Rommel, Nathalie; Tack, Jan; Pauwels, Ans

doi:10.1152/ajpgi.00437.2016

Cited by 23 publications

(17 citation statements)

References 51 publications

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“…Clinical studies have found that CRH within the cerebrospinal fluid was positively correlated with pain perception in patients with chronic pain (McLean et al, 2006 ). A non-selective CRH antagonist decreased pain induced by colonic distension, while intravenous CRH induced esophageal hypersensitivity to distension in healthy volunteers, with no changes in perception of other noxious stimuli (Sagami et al, 2004 ; Broers et al, 2017 ). Intravenous CRH also increased abdominal pain and amygdala blood flow in both healthy volunteers and IBS patients (Tanaka et al, 2016 ).…”

Section: Neurotransmitters In Stress Pathways That Modulate Visceral mentioning

confidence: 99%

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Meerveld

Johnson

2017

Front. Syst. Neurosci.

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Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress-induced exacerbation of chronic visceral pain. Additionally, we will review the importance of specific experimental models of adult stress and ELS in enhancing our understanding of the basic molecular mechanisms of pain processing.

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Section: Neurotransmitters In Stress Pathways That Modulate Visceral mentioning

confidence: 99%

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Meerveld

Johnson

2017

Front. Syst. Neurosci.

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“…A recent study from Belgium demonstrated that intravenous CRH administration increased esophageal sensitivity to mechanical distention in healthy subjects. 11 Our study demonstrated that acute stress, simulated by intravenous CRH, significantly decreased the electrical threshold of esophageal perception. In addition, to the IPT, we also measured ACTH and cortisol levels to verify that subjects were exposed to a true stress load.…”

Section: Discussionmentioning

confidence: 50%

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

Yamasaki

Tomita

Takimoto

et al. 2017

J Neurogastroenterol Motil

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Background/AimsWhen 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. MethodsTwenty 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. ResultsWhen 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. ConclusionIntravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity.

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“…Subsequently, after deflating the balloon, the probe was retracted 10 cm proximal to the LES. More details on the multimodal stimulation test are described elsewhere, briefly; thermal (recirculating a heated solution through the balloon (5 mL NaCl 0.09%, 37‐62°C)), mechanical (balloon distention), electrical (2 stimulation electrodes proximal to the balloon give short electrical block pulses with duration of 1 ms at 200 Hz; maximum current was limited to 40 mA), and chemical sensitivity (0.1 N HCl solution for a maximum period of 30 minutes at 2 mL/min or until pain tolerance threshold is reached) were assessed by this protocol. The positioning and tolerance of the probe are comparable to those of classical esophageal manometry and balloon distention probes …”

Section: Methodsmentioning

confidence: 99%

The optimal order of stimulation modalities and reproducibility of the multimodal esophageal stimulation paradigm

Broers

Boecxstaens

Deloose

et al. 2018

Neurogastroenterology Motil

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Background Esophageal hypersensitivity can be triggered by different stimuli. We use a multimodal stimulation model to study esophageal sensitivity to four sensory modalities: thermal, mechanical, electrical, and chemical stimulation. The optimal order of these stimulations needs further validation. Methods Esophageal sensitivity to thermal (heated saline solution), mechanical (balloon distention), electrical (block pulses with electrodes), and chemical stimulation (acid solution, 0.1 N HCl) was assessed in 10 subjects. In one session, thermal stimulation was performed first, followed by mechanical stimulation (“original protocol”). In a second session, mechanical stimulation was performed first, followed by temperature stimulation (“reversed protocol”). Besides, the impact of balloon distention speed (25 mL/min vs 50 mL/min) during mechanical stimulation was evaluated. Secondly, in order to establish reproducibility, independent control sessions of multimodal stimulations in 15 healthy volunteers were used retrospectively. Key results A significant difference in pain perception threshold for thermal stimulation was found between the original and reversed protocol (P = 0.046), indicating that mechanical stimulation can sensitize the esophagus to thermal stimulation. Balloon distention rate had no impact on sensitivity thresholds for mechanical stimulation. Concerning the reproducibility, there were no differences for thermal, mechanical, electrical, and chemical stimulation in any of the control sessions. Conclusions The optimal order of the multimodal stimulation protocol was to start with the thermal stimulation, followed by mechanical, electrical, and chemical stimulation. The optimal balloon distention rate was 25 mL/min. Multimodal esophageal stimulation generates reproducible perception scores in health and therefore provides a reliable method to assess esophageal sensitivity changes after interventions that may alter esophageal sensitivity.

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The effect of intravenous corticotropin-releasing hormone administration on esophageal sensitivity and motility in health

Cited by 23 publications

References 51 publications

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

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

The optimal order of stimulation modalities and reproducibility of the multimodal esophageal stimulation paradigm

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