Rewiring Chronic Pain

Overview

This study examines the effectiveness of a brief psychological intervention for chronic pain treatment, as well as the psychological and neurophysiological mechanisms associated with changes in pain intensity. Participants with chronic pain will be randomly assigned to one of three groups: two types of brief psychological interventions and a treatment-as-usual control group. Throughout the study, participants will attend a series of therapeutic sessions, complete questionnaires, undergo brain measurements (EEG and MRI), and participate in physiological monitoring using a smartwatch. The study aims to investigate which cognitive and physiological changes occur during the intervention, and whether early markers can be identified that may predict improvement in pain following this type of treatment. In addition, differences between cognitive and somatic components of the intervention will be examined to better understand which elements contribute to clinical change, and to determine whether knowledge alone is sufficient or whether participants must undergo a bodily experience in order to produce changes in pain levels. The goal of the study is to improve understanding of the mechanisms underlying chronic pain and responses to psychological treatments, and to contribute to the development of more personalized, effective treatments with minimal side effects in the future.

Chronic pain is estimated to affect 30% of adults and remains poorly managed by pharmacological approaches, which yield only modest pain reductions (\~0.7-0.9 points on a 0-10 scale) and carry risks of sedation, misuse, and dependence. Short-term psychological interventions, particularly Pain Reprocessing Therapy (PRT), have shown large effects in randomized trials, yet the mechanisms driving their efficacy, and the specific contributions of cognitive versus somatic components, remain unclear. Chronic pain has been consistently associated with structural and functional brain alterations in regions supporting sensory, affective, and interoceptive processing, including the ventromedial prefrontal cortex, anterior cingulate cortex, insula, and nucleus accumbens. Contemporary frameworks (e.g., the dynamic pain connectome) conceptualize chronic pain as a disorder of distributed network dysregulation rather than isolated regional dysfunction, motivating whole-brain functional connectivity, gray matter, and white matter analyses. At the electrophysiological level, slow-wave EEG activity, particularly theta (4-8 Hz) and alpha (8-12 Hz) power, has been linked to low-arousal states induced by hypnosis and mindfulness meditation, both of which produce clinical pain reduction. Animal evidence further links theta activity to neuroplasticity. On this basis, we hypothesize that arousal-state shifts indexed by EEG slow-wave activity and HRV coherence during PRT sessions will predict clinical improvement, and that pre-post MRI will reveal corresponding network and structural changes. The proposed study is a single-blind, three-arm randomized controlled trial that will compare: (1) Full PRT integrating cognitive (psychoeducation) and somatic components (see full protocol at www.painreprocessingtherapy.com/wp-content/uploads/2024/10/PRT-Group-Protocol.pdf); (2) Partial PRT delivering only the cognitive component; and (3) Treatment as Usual (TAU). Both intervention arms will consist of eight 60-minute individual in-person sessions delivered twice weekly by trained providers, with real-time EEG monitoring during each session accessible to the provider to dynamically inform the therapeutic process. Randomization will be stratified by age and medication use, and participants will also be randomly assigned across providers to prevent provider-related confounding. A pilot phase (3-5 participants per intervention arm) will be conducted with EEG but without MRI to refine procedures. Home practice will be standardized within each arm via a unified 8-10 minute audio recording: somatic tracking for the Full PRT arm, and an external-attention mindfulness exercise (sounds, smells, and visual imagery, deliberately avoiding bodily focus) for the Partial PRT arm, isolating the somatic component. Adherence will be self-reported. Assessment will occur at baseline, mid-treatment (abbreviated battery), post-treatment, and at follow-up (MRI up to 6 months; questionnaires up to 5 years). Twice-daily pain ratings and pre/post-session relaxation and valence ratings (0-10) will be collected throughout treatment. Multimodal physiological and neural data will be collected as follows. MRI scans (pre- and post-treatment, \~40 min each) will include high-resolution T1-weighted anatomical imaging, resting-state fMRI, diffusion MRI, and 10 minutes of naturalistic audio-guided fMRI (5 min somatic tracking, 5 min neutral book chapter audio, both with eyes-closed via noise-cancelling headphones). EEG will be recorded during every intervention session using the g.tec Unicorn BCI Core-8 (8 channels, flexible montage). Continuous physiological monitoring via Garmin Vivosmart 5 wearables will capture heart rate variability (beat-to-beat intervals), sleep architecture, and daily activity levels for up to 6 weeks. Blood and saliva samples may also be collected. Analyses will be conducted in Python. Clinical and physiological outcomes will be modeled using Bayesian mixed-effects general linear models to test whether markers of low-arousal states (EEG alpha/theta activity and HRV coherence) predict pain reduction, accounting for repeated measures and covariates. fMRI data will be preprocessed with fMRIPrep and analyzed using parcellation-based connectivity and Network-Based Statistic; structural MRI with FreeSurfer (gray matter volume); diffusion MRI with DIPY (fractional anisotropy); naturalistic fMRI with voxelwise encoding models; and EEG with MNE-Python. Exploratory multivariate prediction of clinical response will use machine learning classifiers.