Brain-network mechanisms underlying the divergent effects of depression on spontaneous versus evoked pain in rats: A multiple single-unit study

Abstract

Studies have reported divergent behavioral effects of depression on spontaneous vs. stimulus-evoked pain. However, the underlying neurobiological mechanisms are still unclear. The present study used a depression model of unpredictable chronic mild stress (UCMS) and pain models for spontaneous pain (i.e., the formalin test) and acute evoked pain (i.e., noxious thermal stimulation) in rats. The activity of neurons within thalamo-cortical circuits in the lateral and medial pain pathways was recorded by a multiple-channel recording technique, and behaviors were observed simultaneously. The results confirmed our previous findings that rats exposed to UCMS tended to exhibit decreased pain sensitivity to experimental stimuli but increased behavioral responses to ongoing pain. Based on the analysis of single-unit responses, the results demonstrated that the processing of spontaneous vs. evoked pain in a depressive-like state was altered in the opposite direction (activation vs. inhibition). The ensemble encoding analysis revealed that exposure to UCMS gave rise to enhanced inter-regional functional connectivity in spontaneous pain processing, but did not influence that of evoked pain. In addition, different brain activation patterns underlying the processing of spontaneous vs. evoked pain were observed. These findings revealed that the distinct response patterns of neurons within the pain-related brain circuits, especially in the affective pain pathway, mediate the divergent effects of depression on spontaneous vs. evoked pain. This is also the first report on the electrophysiology of depression models that provides direct evidence that the effect of depression on spontaneous and evoked pain may involve different brain mechanisms.