Prefrontal cortical hyperactivity in patients with sympathetically mediated chronic pain

Chronic pain continues to impose a large burden of suffering, yet its neural correlates remain poorly understood. In sympathetically mediated chronic pain (SMP), peripheral sympathetic blockade temporarily relieves this pain, so that related neural activity can be studied without perturbing sensory inputs. We used functional magnetic resonance imaging and thermal painful stimuli applied to the chronically painful body site, before and after sympathetic blockade, to examine the cortical network of chronic pain. The chronic SMP state was associated with a widely spread prefrontal hyperactivity, increased anterior cingulate activity and decreased activity in the thalamus contralateral to the body side suffering from SMP, but was unrelated to sensorimotor activity. Ineffective sympathetic blocks, i.e. blocks that did not diminish the SMP pain, did not change the cortical responses to the painful thermal stimulus; while effective placebo resulted in similar responses to those of effective blocks. These findings provide evidence for abnormal brain responses to pain in patients with chronic SMP, which engages prefrontal/limbic networks more extensively than in acute pain-states.