Background & Aims
Visceral pain in disorders of the gut-brain axis is a major cause of disability and healthcare seeking (1). Dynamic learning and memory processes shaping fear of imminent threat are increasingly recognized in the pathophysiology and treatment of chronic visceral pain. In accordance with the fear-avoidance model of pain (2,3), excessive fear-driven avoidance can fuel hypervigilance and hyperalgesia, hamper the adaptive updating of pain-related memories, and hinder exposure-based treatments governed by principles of extinction (4,5). However, despite its profound clinical relevance, the impact of pain-related avoidance on inhibitory learning remains incompletely understood, particularly in visceral pain, in which fear plays a key role (6,7). Implementing an ecologically valid experimental protocol including a pain model and avoidance costs that mimic patients’ clinical reality, we investigated the impact of avoidance on the modulation, including extinction, of visceral pain-related fear.
Methods
Thirty-three healthy volunteers initially underwent an established differential conditioning procedure (8–11) during which rectal distension-induced visceral pain as unconditioned stimulus (US) was repeatedly paired with a visual cue (conditioned stimulus; CS+) while a distinct geometric shape (CS-) remained unpaired. During a subsequent avoidance phase, participants were able to decide whether to avoid or face imminent visceral pain when encountering CS+. An avoidance decision, however, prevented visceral pain in only 50% of trials. In the other half, participants experienced an unpredicted US at a random time point before the next decision, modeling avoidance costs as the confrontation with unexpected pain. A decision to receive pain always resulted in a predicted US. During extinction, all CS were presented unpaired. Behavioral measures of CS valence and fear before and after each experimental phase as well as decisions and reaction times during the avoidance phase were analyzed.
Results
Increased negative valence and fear of CS+ indicated successful differential learning of pain-predictive cue properties. During the avoidance phase, decisions to omit or receive visceral pain depended on the prior pain-related experience. Specifically, participants who decided to face the US and hence receive predicted visceral pain were more likely to repeat than to change their decision. Conversely, the likelihood to avoid was highest after successful avoidance and subsequent pain omission. Reaction times did not differ between decisions. Negative CS+ valence and fear were still increased following avoidance and remained elevated after extinction. Hierarchical regression analyses confirmed that classically-conditioned CS+ valence and fear significantly predicted negative emotional responses after avoidance. Particularly learned fear together with the proportion of avoidance decisions were identified as robust predictors, accounting for 57% of variance in sustained fear of CS+.
Conclusions
This is the first pain-related fear conditioning study applying an ecologically valid visceral pain paradigm to investigate the impact of costly pain avoidance on the persistence and extinction of learned fear of visceral pain. In line with the fear-avoidance model, our findings indicate that successfully exhibited avoidance behaviors providing a short-term pain relief as a form of deceptive safety motivates the maintenance of this behavioral pattern, yet conserves pain-related fear and hampers extinction. Particularly perpetual avoidance behaviors persisting in the absence of threat and often generalizing to non-threatening contexts can increase the risk to encounter unpredictable painful episodes in the future (12). In line with recent evidence, such loss of control and uncertainty may negatively affect the integration and modulation of visceral pain signaling and emotion regulation (9), with profound implications for visceral pain chronicity, psychiatric comorbidity and treatment.
References
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Presenting Author
Adriane Icenhour
Poster Authors
Topics
- Mechanisms: Psychosocial and Biopsychosocial