2020 - Pain

Here, we introduce a new high-dimensional mediation analysis technique to estimate distributed, network-level patterns that formally mediate the relationship between stimulus intensity and pain.

We applied the model to a large-scale analysis of functional magnetic resonance imaging data (N = 284), focusing on brain mediators of the relationship between noxious stimulus intensity and trial-to-trial variation in pain reports.

The new high-dimensional mediation analysis revealed a comprehensive picture of brain responses underlying the complex, multifaceted pain experience. Several brain regions, such as the mPFC, thalamus, NAc, and PBN, are shown to directly and formally mediate stimulus–pain relationships.

Brain mediators predicted pain ratings better than previous brain measures, including the neurologic pain signature (Wager et al. 2013). The functional diversity of the brain mediators observed here offers a better understanding of the brain responses underlying the complexity of the pain experience.