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Pain. 2019 Apr 30. doi: 10.1097/j.pain.0000000000001595. [Epub ahead of print]

Brain moderators supporting the relationship between depressive mood and pain.

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Departments of Neurobiology and Anatomy and.
Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United States.
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Department of Anesthesiology, University of California San Diego, San Diego, CA, United States.


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.

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