Influence of Interoceptive Fear Learning on Visceral Perception

Objectives Interoceptive fear learning and generalization have been hypothesized to play a key role in unexplained abdominal and esophageal pain in patients with functional gastrointestinal disorders. However, there is no experimental evidence demonstrating that fear learning and generalization to visceral sensations can be established in humans and alter visceral perception. Methods In a novel fear learning-generalization paradigm, an innocuous esophageal balloon distension served as conditioned stimulus (CS), and distensions at three different pressure levels around the pain detection threshold were used as generalization stimuli. During fear learning, the CS was paired with a painful electrical stimulus (unconditioned stimulus) in the conditioning group (n = 30), whereas in the control group (n = 30), the unconditioned stimulus was delivered alone. Before and after fear learning, visceral perception thresholds for first sensation, discomfort, and pain and visceral discrimination sensitivity were assessed. Results Fear learning was established in the conditioning group only (potentiated eye-blink startle to the CS (t(464.06) = 3.17, p = .002), and fear generalization to other stimulus intensities was observed (t(469.12) = 2.97, p = .003; t(464.29) = 4.17, p <.001). The thresholds for first sensation habituated in the control group, whereas it remained constant in the conditioning group (F(1,43) = 9.77, p = .003). Conclusions These data show that fear learning using visceral stimuli induces fear generalization and influences visceral perception. These findings support the idea that in functional gastrointestinal disorder, fear learning and generalization can foster gastrointestinal-specific anxiety and contribute to visceral hypersensitivity.