The Neural Basis of Pain Modulation in Depression

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Pain and depression are common, often co-occur in the same patient, and result in significant disability. Over 75% of patients with depression suffer from pain symptoms and between 30-60% of pain patients report significant depressive symptoms. Importantly, the comorbidity between pain and depression contributes significantly to poorer outcomes and increased cost of treatment. Prior work of the applicant during the K99 phase showed that subjects with Major Depressive Disorder (MDD] show increased affective response to experimental pain. This increased affective response was associated with hypersensitivity within emotional processing circuitry and hyposensitivity within emotional regulation circuitry suggesting that MDD impacts pain processing by affectively biasing its perception, which leads to inability to modulate pain experience. Therefore, the integrity of the neural circuits that provide top-down pain modulation is compromised in MDD patients. Two cognitive/affective mechanisms that are important for this top-down modulation include: [1] Pain Anticipation, which enables the brain to alter the processing of pain; and (2] Distraction, which is used by top-down neural substrates to attenuate the experience of pain. The integrity of these processes will be examined using Functional Magnetic Resonance Imaging (fMRI) by comparing individuals with current MDD to healthy subjects. The main goal of the ROO application is to further our understanding of the painrdepression interaction by examining behavior and neural correlates of pain modulation in order to ultimately answer the question "why people feel more pain when they are depressed?" The specific aims are: 1) To assess sensory and affective responses to pain in MDD; 2) To determine which neural substrates underlie anticipation of painful stimulus in MDD; 3] To establish which neural substrates underlie pain modulation by distraction in MDD. Understanding how pain and depression interact will have profound implications for (1) the development of assessments of pain in people at risk for depression; (2) the development of biomarkers for treatment outcomes of pain in depression, (3] the quantification of the emotional effects on pain processes and theirsusceptibility to treatment