The Effects of Corticotropin-Releasing Hormone on Gastric Electrical Activity and Sensorimotor Function in Healthy Volunteers: A Double-blinded Crossover Study

Biopsychosocial factors are associated with disorders of gut brain interaction and exacerbate gastrointestinal symptoms. The mechanisms underlying pathophysiological alterations of stress remain unclear. Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response and has diverse impact on different organ systems. The aim of the present study was to investigate the effects of peripheral CRH infusion on meal-related gastrointestinal symptoms, gastric electrical activity and gastric sensorimotor function in healthy volunteers (HVs). In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effects of CRH on gastric motility and sensitivity. HVs were randomized to receive either peripheral administered CRH (100 µg bolus + 1 µg/kg/hr) or placebo (saline), followed by at least a 7-day washout period and assignment to the opposite treatment. Tests encompassed saliva samples, gastric emptying (GE) testing, body surface gastric mapping (BSGM, Gastric Alimetry®; Alimetry) to assess gastric myoelectrical activity with real-time symptom profiling, and a gastric barostat study to assess gastric sensitivity to distention and accommodation. 20 HVs (13 women, mean age 29.2±5.3 years, BMI 23.3±3.8 kg/m 2 ) completed GE tests, of which 18 also underwent BSGM measurements during the GE tests. The GE half time decreased significantly after CRH exposure (65.2±17.4 vs 78.8±24.5 minutes, p=0.02) with significantly increased gastric amplitude (49.7 (34.7-55.6) vs 31.7 (25.7-51.0) µV, p<0.01), saliva cortisol levels and postprandial symptom severity. Eleven HVs also underwent gastric barostat studies on a separate day. However, the thresholds for discomfort during isobaric distensions, gastric compliance, and accommodation did not differ between CRH and placebo.