Brain moderators supporting the relationship between depressive mood and pain

Abstract

Pain and depressive mood commonly exhibit a comorbid relationship. Yet, the brain mechanisms that moderate the relationship between dysphoric mood and pain remain unknown. An exploratory analysis of functional magnetic resonance imaging, behavioral, and psychophysical data was collected from a previous study in 76 healthy, nondepressed, and pain-free individuals. Participants completed the Beck Depression Inventory-II (BDI), a measure of negative mood/depressive symptomology, and provided pain intensity and pain unpleasantness ratings in response to noxious heat (49°C) during perfusion-based, arterial spin-labeled functional magnetic resonance imaging. Moderation analyses were conducted to determine neural mechanisms involved in facilitating the hypothesized relationship between depressive mood and pain sensitivity. Higher BDI-II scores were positively associated with pain intensity (R = 0.10; P = 0.006) and pain unpleasantness (R = 0.12; P = 0.003) ratings. There was a high correlation between pain intensity and unpleasantness ratings (r = 0.94; P < 0.001); thus, brain moderation analyses were focused on pain intensity ratings. Individuals with higher levels of depressive mood exhibited heightened sensitivity to experimental pain. Greater activation in regions supporting the evaluation of pain (ventrolateral prefrontal cortex; anterior insula) and sensory-discrimination (secondary somatosensory cortex; posterior insula) moderated the relationship between higher BDI-II scores and pain intensity ratings. This study demonstrates that executive-level and sensory-discriminative brain mechanisms play a multimodal role in facilitating the bidirectional relationship between negative mood and pain.

Figure 1

A. Brain activations and deactivations associated with the main effect of pain. Significant activations during painful stimulation were seen in the primary somatosensory cortex (SI) corresponding to the stimulation site, bilateral thalamus, cerebellum, anterior and mid-cingulate cortices, anterior/posterior insula, frontal operculum, secondary somatosensory cortex (SII), supplementary motor area (SMA), and inferior frontal gyrus. Significant deactivations were detected in the bilateral medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), and posterior cingulate cortex (PCC)/precuneus. B. Lower pain intensity ratings associated with higher activation in the inferior parietal lobe. Lower pain intensity reports during noxious heat stimulation were associated with greater activation in the supramarginal gyrus and angular gyrus (p < .001). Slice locations correspond to standard stereotaxic space.

Figure 2.. Brain regions moderating the relationship between depressive mood and pain intensity.

The positive relationship between BDI-II and pain intensity ratings was moderated by high activation [1SD greater than average (+1SD); p < .001] in the contralateral ventrolateral prefrontal cortex (vlPFC), anterior insula, secondary somatosensory cortex (SII), parietal/central operculum, posterior insula during noxious stimulation. Squares (□) are indicative of brain activation 1 SD below the mean (-1SD). Circles (○) are indicative of mean brain activation, and triangles (△) indicate brain activation that is 1 SD greater than the mean. Slice locations correspond to standard stereotaxic space.