Baseline resting-state functional connectivity determines subsequent pain ratings to a tonic ecologically valid...

Pain is a subjective experience with significant individual differences. Laboratory studies investigating pain thresholds and experimental acute pain have identified structural and functional neural correlates. However, these types of pain stimuli have limited ecological validity to real-life pain experiences. Here, we use an orthodontic procedure-the insertion of an elastomeric separator between teeth-which typically induces mild to moderate pain that peaks within 2 days and lasts several days. We aimed to determine whether the baseline structure and resting-state functional connectivity of key regions along the trigeminal nociceptive and pain modulatory pathways correlate with subsequent peak pain ratings. Twenty-six healthy individuals underwent structural and resting-state functional MRI scanning before the placement of a separator between the first molar and second premolar, which was kept in place for 5 days. Participants recorded pain ratings 3 times daily on a 100-mm visual analogue scale. Peak pain was not significantly correlated with diffusion metrics of the trigeminal nerve or gray matter volume of any brain region. Peak pain did, however, positively correlate with baseline resting-state functional connectivity between the thalamus contralateral to the separator and bilateral insula, and negatively correlated with connectivity between the periaqueductal gray (PAG) and core nodes of the default mode network (medial prefrontal and posterior cingulate cortices). The ascending (thalamic) nociceptive and the descending (PAG) pain modulatory pathways at baseline each explained unique variation in peak pain intensity ratings. In sum, preinterventional functional neural architecture of both systems determined the individual pain experience to a subsequent ecologically valid pain stimulus.