Resting-State Functional Connectivity Predicts Individual Pain Ratings to a Tonic Orofacial Pain Stimulus

Pain is a subjective experience with significant individual differences. Laboratory studies investigating pain thresholds and acute pain have identified structural and functional neural correlates. However, these types of pain stimuli have limited ecological validity to real-life pain experience. Here, we use an orthodontic procedure which typically induces pain lasting several days. We aimed to determine whether the baseline structure and resting-state functional connectivity (rsFC) of key regions along the trigeminal nociceptive and pain modulatory pathways correlate with subsequent peak pain ratings. Twenty-six healthy individuals underwent structural (T1, diffusion-weighted MRI) and resting-state functional magnetic resonance imaging (rs-fMRI) scanning prior to the orthodontic procedure, the insertion of an elastomeric separator between teeth, for five days. Participants recorded pain ratings three times, daily. Peak pain was not correlated with structural measures for the trigeminal nerve or any brain region. However, peak pain correlated with rsFC between the contralateral thalamus and bilateral insula, and negatively correlated with connectivity between the periaqueductal gray and core nodes of the default mode network (medial prefrontal and posterior cingulate cortices). In this ecologically valid model, we demonstrate that both ascending nociceptive and descending pain modulatory pathways shape the individual pain experience.