Background & Aims

Expectation can greatly impact our physiological and psychological states, influencing our behavior and decision making(1). The threat of pain can elicit physiological arousal, which is related to activation of the sympathetic nervous system(2) and has been linked to anxiety and fear(3,4). Youth with anxiety experience increased sympathetic arousal in anticipation of cued heat-pain in comparison to youth without anxiety, despite pain not differing between groups(5). These differences may reflect general threat processing or could be specific to pain. Our goal was to compare sympathetic arousal during the anticipation of painful aversive heat with non-painful aversive stimulation (unpleasant taste), as well as appetitive stimulation (pleasant taste), as arousal is independent of valence. We hypothesized that sympathetic arousal would be greater during 1) the anticipation of aversive versus appetitive stimuli, and 2) the anticipation of high intensity versus low intensity stimuli.

Methods

Following a calibration visit, 60 healthy volunteers were randomly assigned to 1 of 3 stimulus groups (Heat, Salt, Sugar). In each of 60 trials, participants saw a 2-second cue that predicted either a high or low intensity stimulus, followed by a 2-3 second window of anticipation before the stimulus was delivered. Painful heat stimulation was administered with a thermode, while the appetitive (sugar solution) and non-painful aversive (salt solution) stimuli were delivered through a feeding tube. Skin conductance, a measure of sympathetic arousal(6), was collected continuously. We analyzed skin conductance responses (SCRs) within the anticipatory window in 45 volunteers with reliable skin conductance (14 Heat, 14 Salt, 17 Sugar). SCRs were scored with Ledalab(7) and average SCR per participant was calculated as the dependent variable. A mixed factorial ANOVA design was used to analyze effects of Group and Cue on Average SCR with Bonferroni correction for post-hoc multiple comparisons.

Results

In contrast to our hypothesis regarding anticipation of high relative to low stimuli, we did not observe any main effects of Cue (p > 0.6), nor any interactions between Group and Cue (p > 0.14). However, a marginal main effect of Group was identified (p = 0.055), leading us to perform a post-hoc pairwise t-test on Average SCR by Group during anticipation. The post-hoc pairwise t-test revealed that the average skin conductance recorded during the anticipation of heat (M = 0.11, SD = 0.11) was significantly greater than during the anticipation of salt (M = 0.02, SD = 0.03; p < 0.001). No significant differences were identified between the anticipation of heat and sugar or the anticipation of salt and sugar.

Conclusions

We found that anticipation of heat had a greater influence on arousal than the anticipation of salt, independent of Cue. Interestingly, behavioral analyses suggested that salt was perceived as more intense than heat, although they were rated as equally unpleasant. This might suggest that the anticipation of painful aversive stimuli is viewed as a greater threat than non-painful aversive stimuli, leading to an increase in sympathetic arousal. However, it is unknown whether these findings would generalize to other forms of painful stimuli and how anticipatory arousal of heat compares to that of other pain modalities. Future studies should include comparisons of other painful aversive stimuli (e.g., pressure, shock, cold, etc.) to assess if the pattern of sympathetic arousal during anticipation found in this study is specific to heat pain.

References

1. Schwarz, K. A., Pfister, R., & Büchel, C. (2016). Rethinking explicit expectations: connecting placebos, social cognition, and contextual perception. Trends in cognitive sciences, 20(6), 469-480.Baldwin, (2013). Neuroscience & Biobehavioral Reviews

2. Peifer, C., Schulz, A., Schächinger, H., Baumann, N., & Antoni, C. H. (2014). The relation of flow-experience and physiological arousal under stress—can u shape it?. Journal of Experimental Social Psychology, 53, 62-69.

3. Rozenman, M., Vreeland, A., & Piacentini, J. (2017). Thinking anxious, feeling anxious, or both? Cognitive bias moderates the relationship between anxiety disorder status and sympathetic arousal in youth. Journal of Anxiety Disorders, 45, 34-42.

4. Ochsner, K. N., Ludlow, D. H., Knierim, K., Hanelin, J., Ramachandran, T., Glover, G. C., & Mackey, S. C. (2006). Neural correlates of individual differences in pain-related fear and anxiety. Pain, 120(1-2), 69-77.

5. Abend, R., Bajaj, M. A., Harrewijn, A., Matsumoto, C., Michalska, K. J., Necka, E., … & Pine, D. S. (2021). Threat-anticipatory psychophysiological response is enhanced in youth with anxiety disorders and correlates with prefrontal cortex neuroanatomy. Journal of Psychiatry and Neuroscience, 46(2), E212-E221.

6. Wickramasuriya, D. S., & Faghih, R. T. (2020). A marked point process filtering approach for tracking sympathetic arousal from skin conductance. IEEE Access, 8, 68499-68513.

7. Benedek, M., & Kaernbach, C. (2010). A continuous measure of phasic electrodermal activity. Journal of neuroscience methods, 190(1), 80-91.

Presenting Author

Kai Sherwood

Poster Authors

Kai Sherwood

BS

National Institutes of Health (NIH)

Lead Author

Yili Zhao

PhD

National Center for Complementary and Integrative Health, National Institutes of Health

Lead Author

In-Seon Lee

PhD

Kyung Hee University: Department of Science in Korean Medicine

Lead Author

Margaret Rose-McCandlish

BA

National Institutes of Health (NIH), Indiana University Indianapolis

Lead Author

Qingbao Yu

National Institutes of Health (NIH)

Lead Author

Lauren Atlas

PhD

National Institutes of Health (NIH)

Lead Author

Topics

  • Mechanisms: Psychosocial and Biopsychosocial