Contingency Awareness Shapes Acquisition and Extinction of Emotional Responses in a Conditioning Model of Pain-Related Fear

Abstract

As a fundamental learning process, fear conditioning promotes the formation of associations between predictive cues and biologically significant signals. In its application to pain, conditioning may provide important insight into mechanisms underlying pain-related fear, although knowledge especially in interoceptive pain paradigms remains scarce. Furthermore, while the influence of contingency awareness on excitatory learning is subject of ongoing debate, its role in pain-related acquisition is poorly understood and essentially unknown regarding extinction as inhibitory learning. Therefore, we addressed the impact of contingency awareness on learned emotional responses to pain- and safety-predictive cues in a combined dataset of two pain-related conditioning studies. In total, 75 healthy participants underwent differential fear acquisition, during which rectal distensions as interoceptive unconditioned stimuli (US) were repeatedly paired with a predictive visual cue (conditioned stimulus; CS+) while another cue (CS−) was presented unpaired. During extinction, both CS were presented without US. CS valence, indicating learned emotional responses, and CS-US contingencies were assessed on visual analog scales (VAS). Based on an integrative measure of contingency accuracy, a median-split was performed to compare groups with low vs. high contingency accuracy regarding learned emotional responses. To investigate predictive value of contingency accuracy, regression analyses were conducted. Highly accurate individuals revealed more pronounced negative emotional responses to CS+ and increased positive responses to CS− when compared to participants with low contingency accuracy. Following extinction, highly accurate individuals had fully extinguished pain-predictive cue properties, while exhibiting persistent positive emotional responses to safety signals. In contrast, individuals with low accuracy revealed equally positive emotional responses to both, CS+ and CS−. Contingency accuracy predicted variance in the formation of positive responses to safety cues while no predictive value was found for danger cues following acquisition and for neither cue following extinction. Our findings underscore specific roles of learned danger and safety in pain-related acquisition and extinction. Contingency accuracy appears to distinctly impact learned emotional responses to safety and danger cues, supporting aversive learning to occur independently from CS-US awareness. The interplay of cognitive and emotional factors in shaping excitatory and inhibitory pain-related learning may contribute to altered pain processing, underscoring its clinical relevance in chronic pain.

Associative learning and extinction of conditioned threat predictors across sensory modalities

“…Statistical analyses of the accuracy of CS–US associations require more complex computations (for an approach, see ref. 112 ), which is beyond the scope herein.…”

Enhanced pain-related conditioning for face compared to hand pain

“…Interestingly, contingency, but not valence ratings differed after the extinction phase between both pain conditions, indicating that these emotional and cognitive aspects related to pain learning may not develop uniformly and represent related, yet separate processes [31,71]. Taken together, face pain seems to elicit higher pain-related fear [27,63] and negative emotions, defensive responses [29], and, as shown here at least at trend level with medium effect sizes, increased contingency awareness.…”

From gut feelings to memories of visceral pain

“…These include predictability as well as the conscious awareness of CS-US contingenciesaspects that remain incompletely understood in the context of pain. In light of first data supporting altered contingency learning and extinction in patients with chronic pain (Icenhour et al, 2015b;Meulders et al, 2014), we elucidated the putative role of contingency awareness in shaping the acquisition and extinction of conditioned emotional responses in a large sample of healthy volunteers (Labrenz et al, 2015). Herein, participants with highly accurate contingency awareness revealed greater emotional learning toward both danger as well as safety cues.…”