Cortico-Limbic Circuitry in Chronic Pain Tracks Pain Intensity Relief Following Exposure In Vivo

Abstract Background A subset of patients with chronic pain who receive Exposure in vivo (EXP) treatment experience clinically-relevant pain intensity relief. Although pain relief is no explicit therapeutic target, it is important to understand how and why this concomitant effect occurs in some but not others. This longitudinal study therefore aims to characterize brain plasticity as well as to explore pre-treatment factors related to pain relief. Methods Resting-state fMRI data were acquired in 30 patients with chronic pain. Twenty-three patients completed EXP, and six-month follow-up data was available in n=20 (MRI data in n=17). Pain-free control data were acquired at two time-points (n=29, n=21). Seed-based resting-state functional connectivity (rsFC) analyses were performed, with seeds in amygdala, hippocampus and nucleus accumbens. Results Pain relief following EXP was highly variable, with 60% of patients reporting a clinically-relevant improvement. Amygdala rsFC with middle frontal gyrus decreased significantly over time in patients, not associated with pain relief. In contrast, greater pain relief was associated with greater decreases over time in hippocampus rsFC with precuneus, which was related to reductions in catastrophizing (EXP therapeutic target) too. Greater pain relief was also associated with lower pre-treatment nucleus accumbens rsFC with postcentral gyrus. Conclusion While changes in hippocampus rsFC were associated with pain relief following EXP, pre-treatment nucleus accumbens rsFC showed potential prognostic value. Our findings further support the importance of cortico-limbic circuitry in chronic pain, emphasizing its relation to pain relief and identifying potential underlying mechanisms and prognostic factors, warranting further testing in independent samples.