• Erik Ceunen, Jonas Zaman, Nathalie Weltens, Ekaterina Sarafanova, Vicky Arijs, Johan W S Vlaeyen, Lukas Van Oudenhove, and Ilse Van Diest.
• Health Psychology, KU Leuven, Leuven, Belgium.
• Clin. Gastroenterol. Hepatol. 2016 Nov 1; 14 (11): 1552-1558.e2.

Background & AimsGastrointestinal symptom-specific fear and anxiety are important determinants of gastrointestinal symptom perception. We studied learning of fear toward innocuous gastrointestinal sensations as a putative mechanism in the development of gastrointestinal symptom-specific fear and anxiety.MethodsFifty-two healthy subjects (26 women) received 2 types of esophageal balloon distention at a perceptible but nonpainful intensity (conditioned stimulus [CS], the innocuous sensation) and at a painful intensity (unconditioned stimulus [US]). Subjects were assigned randomly to 1 of 2 groups. During the learning phase, the innocuous CS preceded the painful US in the experimental group (n = 26). In the control group (n = 26), on the contrary, the US never followed the CS directly. During a subsequent extinction phase, both groups received only CS distention-the painful US was no longer administered. Indexes of fear learning toward the innocuous CS distention included the skin conductance response, fear-potentiated startle (measured by the eye-blink electromyogram), and self-reported expectancy of the US.ResultsDuring the learning phase, only the experimental group learned to fear the innocuous gastrointestinal CS, based on the increase in US expectancy (compared with the control group, P = .04), increased skin conductance response (compared with the control group, P = .03), and potentiated startle reflex (compared with the control group, P = .001) in response to the CS. The differences between the experimental and control groups in US expectancy and skin conductance, but not fear-potentiated startle, disappeared during the extinction phase.ConclusionsFear toward innocuous gastrointestinal sensations can be established through associative learning in healthy human beings. This may be an important mechanism in the development of fear of gastrointestinal symptoms, implicated in the pathophysiology of functional gastrointestinal disorders.Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

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