By Karla Gale

NEW YORK (Reuters Health) - Patients with major depressive disorder experience abnormally high emotional reactivity during anticipation of pain that impairs their ability to modulate the actual pain experience, according to evidence from a functional magnetic resonance neuroimaging study.

These altered neurophysiological responses may mediate the high comorbidity of chronic pain conditions and depression, the study authors report in the November issue of the Archives of General Psychiatry.

"We recently showed that the emotional component of the pain response is enhanced in people who are depressed," lead author Dr. Irina A. Strigo, at the University of California San Diego, La Jolla, said in an interview with Reuters Health. "Based on that, we hypothesized that emotion-processing areas of the brain would be hyperresponsive in these people during experimental pain."

"The far-reaching goal of this research," she added, "is to find treatments that can prevent depressed people from developing chronic pain conditions, and to find treatments that can prevent chronic pain patients from developing major depressive disorder."

Their study included 15 subjects with major depressive disorder, ages 18 to 35, who were otherwise healthy, and 15 control subjects with no history of psychiatric illness. The experimental protocol involved painfully hot and non-painful warm stimuli to the subjects' left forearm 20 times in a pseudo-random order. At 4-8 seconds prior to the stimulus, subjects were cued by a color change projected on a screen (red = anticipate pain, green = anticipate warmth).

Blood oxygen level-dependent functional MRI scans were obtained during anticipation and processing of painful and non-painful stimuli.

In depressed subjects, activation of the amygdala, the anterior cingulate cortex and the anterior insular region was increased during pain anticipation, which the authors suggest "may represent a neural correlate of hypervigilant monitoring of negative information."

During the actual painful event, however, regions of the prefrontal cortex, the rostral anterior cingulate, and the periaqueductal gray matter were less activated than in healthy subjects, even though the perception of pain intensity did not differ between groups.

"It seems that an increased anticipatory reaction to an upcoming painful stimulus causes a state of catastrophizing and helplessness, so that the patient doesn't try to control the actual pain experience," Dr. Striga explained.

These findings are important in developing therapeutic techniques for patients with depression and chronic pain, co-author Dr. Alan N. Simmons told Reuters Health.

"We found that brain areas that show strong relationship to body sense are important in this anticipatory process," he said. "That means that people have the opportunity to learn techniques to change the way the body is feeling during the anticipatory periods when they don't have a direct negative stimulus to deal with. That can have more impact on the person than what they do during the actual negative event."

Cognitive behavioral techniques, such as breathing retraining, muscle relaxation, and music therapy, may be effective, Dr. Simmons added, "because those are not necessarily the things that one does during the experience, but things to do in preparation or in dealing with repercussions of things that are emotionally or physically distressing."

Arch Gen Psychiatry 2008;65:1275-1284.

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