Chronic pain and substance dependency are characterized by a more predictive and stronger connectivity in the amygdala within the theta/alpha band

Introduction: Individuals with chronic pain and substance abuse demonstrate altered pain processing. However, the underlying neurocircuitry remains poorly understood. Our study explores neuronal signals within the limbic system that may shed light on pain perception in these groups.

Methods: We recorded local field potentials (LFPs) from 15 epilepsy patients with intracranial depth electrodes implanted for seizure monitoring (at 200Hz). Regions studied included the amygdala (N=12), hippocampus (N=15), dorsolateral prefrontal cortex/DLPFC (N=8), anterior cingulate cortex/ACC (N=7), orbitofrontal cortex/OFC (N=9), insula (N=8), and ventrolateral prefrontal cortex/VLPFC (N=11).
LFPs were extracted for 15 minutes prior to administration of pain medications and filtered within the theta and alpha range (4-12 Hz). Signals were compared between patients with drug abuse and/or chronic pain (DU/CP; N=8) and those without (N=7). Auto-mutual information (AMI), a nonlinear metric akin to cross-correlation, was computed for each of these seven regions individually. To assess connectivity, we analyzed cross-correlation between the enveloped time series from the right and left sides of these seven regions.

Results: We observed that pain medications were more frequently administered to DU/CP patients, suggesting their altered pain processing. In these subjects, we observed increased predictive information within the amygdala (p < 0.05) and marginal predictiveness in the VLPFC (p < 0.1). Additionally, we found stronger connectivity between the left and right amygdala (p < 0.05). Conversely, DU/CP patients exhibited weaker connectivity between the right ACC and right DLPFC (p < 0.05).

Conclusion : In DU/CP patients, the amygdala was characterized by both local predictive signals and robust bilateral connectivity, and weaker connectivity in the ACC-DLPFC. We interpret our findings as indicative of the role of an amygdala-ACC-DLPFC circuit in pain processing. We aim to validate these findings with future experiments.