Pain‐free default mode network connectivity contributes to tonic experimental pain intensity beyond the role of negative mood and other pain‐related factors

Background: Alterations in the default mode network (DMN) connectivity across pain stages suggest a possible DMN involvement in the transition to persistent pain. Aim: This study examined whether pain-free DMN connectivity at lower alpha oscillations (8-10 Hz) accounts for a unique variation in experimental peak pain intensity beyond the contribution of factors known to influence pain intensity. Methods: Pain-free DMN connectivity was measured with electroencephalography prior to 1 h of capsaicin-evoked pain using a topical capsaicin patch on the right forearm. Pain intensity was assessed on a (0–10) numerical rating scale and the association between peak pain intensity and baseline measurements was examined using hierarchical multiple regression in 52 healthy volunteers (26 women). The baseline measurements consisted of catastrophizing (helplessness, rumination, magnification), vigilance, depression, negative and positive affect, sex, age, sleep, fatigue, thermal and mechanical pain thresholds and DMN connectivity (medial prefrontal cortex [mPFC]-posterior cingulate cortex [PCC], mPFC-right angular gyrus [rAG], mPFC-left Angular gyrus [lAG], rAG-mPFC and rAG-PCC). Results: Pain-free DMN connectivity increased the explained variance in peak pain intensity beyond the contribution of other factors (ΔR 2 = 0.10, p = 0.003), with the final model explaining 66% of the variation (R 2 = 0.66, ANOVA: p < 0.001). In this model, negative affect (β = 0.51, p < 0.001), helplessness (β = 0.49, p = 0.007), pain-free mPFC-lAG connectivity (β = 0.36, p = 0.003) and depression (β = −0.39, p = 0.009) correlated significantly with peak pain intensity. Interestingly, negative affect and depression, albeit both being negative mood indices, showed opposing relationships with peak pain intensity. Conclusions: This work suggests that pain-free mPFC-lAG connectivity (at lower alpha) may contribute to individual variations in pain-related vulnerability. Significance: These findings could potentially lead the way for investigations in which DMN connectivity is used in identifying individuals more likely to develop chronic pain.