Background & Aims
Expectations substantially shape human pain perception (Atlas, 2023). In chronic pain conditions, patients frequently exhibit both abnormal affective states and aberrant pain expectations (Bushnell et al., 2013), which suggests that an individual’s emotional states may substantially influence the effect of expectations on pain processing. However, how an individual’s emotions bias this pain modulatory process remains unclear. The present study aimed to explore the neural basis underlying the effect of an individual’s emotions on pain modulation by stimulus expectancy. Given our recent study indicates that expectation- and stimulus-associated emotions integrate expectations and sensory inputs to form pain perception (emotion integration model; Tsai et al., 2024), we hypothesized that either the valence (positive or negative; valence hypothesis) or the arousal level (arousal hypothesis) of an individual’s emotions would bias stimulus expectancy effects on pain.
Methods
In a cue-based stimulus expectancy paradigm established in our lab (Shih et al., 2019), we used emotional pictures (selected from the International Affective Picture System; Lang et al., 2008) to induce different emotional states in 32 healthy volunteers when they anticipated upcoming painful electrical stimulation. Based on the emotion integration model we reported previously (Tsai et al., 2024), we incorporated a parameter into the model to account for individual susceptibility to emotional stimuli during pain modulation by stimulus expectancy. This parameter was estimated via maximum likelihood estimation in each participant and then utilized as a covariate of interest in imaging analyses to explore neural substrates accounting for emotional modulation on pain expectancy effects. A Bayesian model selection approach (Tsai et al., 2024) was applied for model comparisons using valence-sensitive and arousal-sensitive parameters.
Results
Behaviorally, we observed that positive expectations (expectations of reduced pain) significantly attenuated participants’ pain perception across all three emotional conditions. Compared to neutral pictures, the extent of pain reduction was significantly smaller when participants viewed emotional (pleasant and unpleasant) pictures, with no significant difference in pain reduction between pleasant and unpleasant pictures. Bayesian model comparison analyses further confirmed that the arousal model better explained the modulation of emotion on pain expectancy effects compared to the valence model. Neurally, we found that the periaqueductal gray (PAG) encoded the estimated individual susceptibility to emotional arousal when stimulus expectancy influenced pain perception. In other words, participants with stronger activation in the PAG showed a more pronounced impact of emotional arousal on pain modulation by stimulus expectancy.
Conclusions
Our findings suggest that the arousal level of an individual’s emotions biases stimulus expectancy effects on pain, which is implemented in the brainstem pain-modulating center. These findings enhance current understanding about the complex interaction between emotion and cognition during pain processing. Investigations on how an individual’s affective state influences expectation-associated pain modulation can help explain why subjects with chronic pain exhibit dysregulated expectations for pain and pain processing, and frequently experience comorbid mood disorders.
References
Atlas LY. How Instructions, Learning, and Expectations Shape Pain and Neurobiological Responses. Annu Rev Neurosci. 2023;46:167-189.
Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 2013;14(7):502-11.
Lang PJ, Bradley MM, Cuthbert BN (2008) International affective picture system (IAPS): Affective ratings of pictures and instruction manual. Technical Report A-8. University of Florida, Gainesville, FL.
Shih YW, Tsai HY, Lin FS, Lin YH, Chiang CY, Lu ZL, Tseng MT. Effects of Positive and Negative Expectations on Human Pain Perception Engage Separate But Interrelated and Dependently Regulated Cerebral Mechanisms. J Neurosci. 2019;39(7):1261-1274.
Tsai HY, Lapanan K, Lin YH, Huang CW, Lin WW, Lin MM, Lu ZL, Lin FS, Tseng MT. Integration of Prior Expectations and Suppression of Prediction Errors During Expectancy-Induced Pain Modulation: The Influence of Anxiety and Pleasantness. J Neurosci 44 (17) e1627232024.
Presenting Author
Ming-Tsung Tseng
Poster Authors
Topics
- Pain Imaging