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Deceptive safety? The impact of costly pain avoidance on the modulation and extinction of visceral pain-related fear

Labrenz, F.; Kalenbach, A.; Elsenbruch, S.; Icenhour, A.

2025-06-25 neuroscience
10.1101/2025.06.25.661529 bioRxiv
Show abstract

Along the gut-brain axis, visceral pain demonstrably evokes emotional learning and memory processes shaping behavior in clinically relevant ways. Avoidance motivated by learned fear may constitute a major obstacle to treatment success in extinction-based interventions. However, the effects of avoidance on visceral pain-related fear extinction remain poorly understood. By implementing an ecologically valid experimental protocol, we investigated how costly avoidance affects the modulation and extinction of visceral pain-related fear. Thirty-three healthy volunteers underwent conditioning with visual cues (conditioned stimuli; CS+,CS-) consistently followed by visceral pain or remaining unpaired. During avoidance, participants decided to avoid or receive pain upon confronting CS+. Avoidance decisions resulted in pain omission in some trials, while in others, participants experienced unpredictable pain. During extinction, CS were presented unpaired. CS valence, fear, and trial-by-trial decisions were analyzed. Avoidance decisions depended on prior experiences, with the highest probability of avoidance following successful pain omission. Negative CS+ valence and fear remained elevated across avoidance and extinction. Learned fear and more avoidance decisions explained 57% variance in sustained CS+ fear. Our findings indicate that avoidance, which provides short-term absence of pain even when followed by unpredictable pain, motivates its maintenance. However, it perpetuates pain-related fear and may impede extinction, with implications for persisting symptoms and therapeutic outcomes in chronic visceral pain.

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