Individual differences in conditioned pain modulation are associated with alpha oscillations

Conditioned pain modulation (CPM), the change in pain evoked by a test stimulus at 1 body site by a conditioning stimulus at another site, varies across individuals, ranging from inhibition (pain decreases) to no CPM to facilitation (pain increases). Given the role of alpha oscillations in pain, we examined the relationship between CPM and peak alpha frequency (PAF) and power in the dynamic pain connectome (DPC). In 68 healthy individuals who underwent resting-state magnetoencephalography and a heat-based CPM evaluation, 32% had inhibitory CPM, 49% had facilitatory CPM, and 19% had no CPM. The facilitatory subgroup had lower alpha power in the medial prefrontal cortex (mPFC) compared with the inhibitory subgroup and across the DPC (mPFC, right thalamus, bilateral dorsolateral prefrontal cortex [dlPFC]) compared with the noCPM subgroup. Peak alpha frequency in the thalamus bilaterally was strongly correlated with inhibitory CPM (higher PAF with stronger inhibitory CPM). The subgenual anterior cingulate cortex (sgACC) PAF was correlated with inhibitory CPM in males and females in opposite directions, but not at the whole subgroup level. The pressure-based CPM evoked inhibitory CPM in 87% of the 45 individuals tested; the relationship with PAF in the right dlPFC and sgACC had medium-strong effect sizes driven by males (higher PAF with weaker inhibitory CPM). This study indicates that the role of alpha oscillations in CPM is paradigm- and sex-dependent. Our findings that healthy individuals exhibit an alpha-CPM relationship, particularly in the prefrontal regions and sgACC, provide insight into the potential therapeutic use of targeted neuromodulation for pain.