Depressed Patients Have Dysfunctional Pain-Processing Network

By Todd Neale
LA JOLLA, Calif.,09 nov 2008 -- Patients with major depressive disorder process pain differently in the brain than healthy individuals, researchers here found.
During exposure to a painful heat stimulus, depressed patients had decreased activity in the area of the brain responsible for pain modulation, Irina Strigo, Ph.D., of the University of California San Diego, and colleagues reported in the November issue of Archives of General Psychiatry.
When the same patients anticipated pain, they had increased activity in the right anterior insular region, dorsal anterior cingulate, and right amygdala, parts of an emotion-processing network.
"The anticipatory brain response may indicate hypervigilance to impending threat, which may lead to increased helplessness and maladaptive modulation during the experience of heat pain," the researchers said.
"This mechanism could in part explain the high comorbidity of pain and depression when these conditions become chronic," they said.
More than three-quarters of patients with depression have chronic pain and 30% to 60% of patients with chronic pain have depressive symptoms, according to the researchers.
But despite the overlap between the two conditions, they said, little is known about the neurobiological basis of how pain is processed in the brains of patients with major depressive disorder.
So they recruited 15 patients with major depressive disorder (12 females; mean age 24.5) and 15 healthy controls with no history of psychiatric disorders (10 females; mean age 24.3) to undergo functional magnetic resonance imaging before and during painful stimulation.
The depressed patients completed the Pain Catastrophizing Scale, which assesses magnification, rumination, and helplessness related to pain.
Both painful and non-painful levels of heat were applied to the participants' forearms as they viewed images that signaled the intensity of heat to come.
The temperatures did not differ significantly between the groups; the painful stimulus was 115.5° F in the depressed patients and 116.4° F for the controls (P=0.08), and the non-painful stimulus was 102.2° F for both groups (P=0.59).
Both groups reported similar subjective ratings of the unpleasantness and intensity of the painful heat.
The depressed patients rated the non-painful heat as significantly more unpleasant (P=0.04), "a finding that is consistent with our previous observations of the increased affective bias in major depressive disorder at non-painful temperatures," the researchers said.
During the anticipation of pain, the depressed patients had increased activation in the right anterior insular region, left anterior insular/inferior frontal gyrus, bilateral dorsal anterior cingulate cortex, right dorsolateral prefrontal cortex, several clusters in the left dorsolateral prefrontal cortex, clusters in the temporal and occipital lobes, and right amygdala.
The increased activity in the amygdala during anticipation was associated with greater levels of perceived helplessness toward pain (P=0.01) and rumination (P=0.02) in the depressed patients only.
During painful stimulation, the depressed patients had increased activity in the left parahippocampal gyrus and occipital cortex and the right amygdala, and decreased activity in the periaqueductal gray matter and the rostral anterior cingulate and prefrontal cortices.
The increased activity in the amygdala during painful stimulation was associated with perceived levels of helplessness (P=0.02) and rumination (P=0.03).
"These findings suggest that increased emotional reactivity during the anticipation of heat pain may lead to an impaired ability to modulate pain experience in major depressive disorder," the researchers said.
Cognitive models suggest that patients with major depressive disorder negatively bias their expectations, perceptions, and memories, which may lead to the development of passive coping styles that promote helplessness and the maintenance of depression, they said.
Past studies have shown that passive coping styles are associated with the enhanced emotional impact of chronic and experimental pain.
The current findings are in line with these models, the researchers said, and "may represent a neural correlate of hypervigilant monitoring of negative information in major depressive disorder," the researchers said.
The authors acknowledged that the study was limited by the "mixed sample of relatively modest size," and that the findings needed to be confirmed using more patients.
The study was supported by grants from the National Institute of Mental Health and by the Barrow Neurological Foundation, the National Alliance for Research in Schizophrenia and Depression, and the University of California San Diego Center of Excellence for Stress and Mental Health.
The authors reported no financial disclosures.
Primary source: Archives of General PsychiatrySource reference:Strigo I, et al "Association of major depressive disorder with altered functional brain response during anticipation and processing of heat pain"Arch Gen Psychiatry 2008; 65: 1275-1284.