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Irina A. Strigo, PhD; Alan N. Simmons, PhD; Scott C. Matthews, MD; Arthur D. (Bud) Craig, PhD; Martin P. Paulus, MD

Arch Gen Psychiatry. 2008;65(11):1275-1284.

Context  Chronic pain and depression are highly comorbid conditions, yet little is known about the neurobiological basis of pain processing in major depressive disorder (MDD).

Objective  To examine the neural substrates underlying anticipation and processing of heat pain in a group of unmedicated young adults with current MDD.

Design  Functional magnetic resonance neuroimaging data were collected during an event-related factorial experimental pain paradigm. Painful and nonpainful heat stimuli were applied to the left volar forearm while different color shapes explicitly signaled the intensity of the upcoming stimulus.

Setting  University brain imaging center.

Patients  Fifteen (12 female) young adults with current MDD and 15 (10 female) healthy subjects with no history of MDD were recruited and matched for age and level of education. The Structured Clinical Interview for DSM-IV was administered to all participants by a board-certified psychiatrist.

Main Outcome Measure  Between-group differences in blood oxygen level–dependent functional magnetic resonance neuroimaging signal change to anticipation and processing of painful vs nonpainful temperature stimuli.

Results  Subjects with MDD compared with healthy controls showed (1) increased activation in the right anterior insular region, dorsal anterior cingulate, and right amygdala during anticipation of painful relative to nonpainful stimuli, (2) increased activation in the right amygdala and decreased activation in periaqueductal gray matter and the rostral anterior cingulate and prefrontal cortices during painful stimulation relative to nonpainful stimulation, and (3) greater activation in the right amygdala during anticipation of pain, which was associated with greater levels of perceived helplessness.

Conclusions  These findings suggest that increased emotional reactivity during the anticipation of heat pain may lead to an impaired ability to modulate pain experience in MDD. Future studies should examine the degree to which altered functional brain response during anticipatory processing affects the ability to modulate negative affective states in MDD, which is a core characteristic of this disorder.

Author Affiliations: University of California San Diego, La Jolla (Drs Strigo, Simmons, Matthews, and Paulus) and Psychiatry Service, San Diego Veterans Affairs Medical Center, San Diego (Drs Matthews and Paulus); and Division of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona (Drs Strigo and Craig).

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