Riding The Waves of Pain: The Neural Correlates and Impact of Day-to-Day Pain Fluctuations on Clinical Outcomes after Cognitive Behavioral Therapy

Pain is a subjective, multifaceted experience that varies substantially between and within chronic pain patients and is characterized by somatosensory, affective, and cognitive components. However, whether high day-to-day fluctuation amplitude (“hope for change”) or low amplitude/consistent pain experience (“know what to expect”) contributes to better or worse therapeutic outcomes is an ongoing debate. In this longitudinal MRI study involving an 8-week cognitive behavioral therapy (CBT) intervention in Fibromyalgia patients (N=61, all female, age (SD) = 41.27 (12.54) years), the impact of baseline daily reported pain fluctuations, i.e., standard deviation, on brain responses to nociceptive stimuli and clinical outcomes were investigated. Patients either received CBT or a duration-matched education-control (EDU). Preceding the intervention, patients underwent an evoked pressure pain paradigm during whole-brain fMRI (Siemens 3T-MRI, TR/TE=1250/33ms, voxel size 2mm3 isotropic, SMS MB acc. factor 5). Thetask included six leg cuff stimulations of either non- or moderately painful pressures (calibrated to individual’s threshold). Clinical outcomes were assessed using the Pain Catastrophizing Scale (PCS), a specific target of CBT. Greater baseline day-to-day clinical pain fluctuations were associated with greater post-therapy improvement in pain catastrophizing in the CBT but not the EDU group. Furthermore, greater day-to-day clinical pain fluctuations were negatively correlated with BOLD-fMRI responses during pain anticipation in nociceptive processing areas (i.e., primary-somatosensory-cortex, insula, and superior-parietal-lobule). The results suggest that greater clinical pain fluctuations may boost clinical treatment effects by influencing anticipation of pain. Importantly, this study highlights the predictive importance of clinical pain variability in longitudinal interventional research involving chronic pain populations. Funding: R01-AT-007550, R33-AT-009306, P01-AT-009965, R01-AR-064367, R01-AR-079110, P41-RR-14075, S10-RR-021110, S10-RR-023043, R01-AT-012144.