Abstract
Placebo has been reported to exert beneficial effects in patients regarding the treatment of pain. Human functional neuroimaging technology can study the intact human brain to elucidate its functional neuroanatomy and the neurobiological mechanism of the placebo effect. Blood flow measurement using functional magnetic resonance imaging and positron emission tomography (PET) has revealed that analgesia is related to decreased neural activities in pain-modulatory brain regions, such as the rostral anterior cingulate cortex (rACC), insula, thalamus, and brainstem including periaqueductal gray (PAG) and ventromedial medulla. The endogenous opioid system and its activation of mu-opioid receptors are thought to mediate the observed effects of placebo. The mu-opioid receptor-selective radiotracer-labeled PET studies show that the placebo effects are accompanied by reduction in activation of opioid neural transmission in pain-sensitive brain regions, including rACC, prefrontal cortex, insula, thalamus, amygdala, nucleus accumbens (NAC) and PAG. Further PET studies with dopamine D2/D3 receptor-labeling radiotracer demonstrate that basal ganglia including NAC are related to placebo analgesic responses. NAC dopamine release induced by placebo analgesia is related to expectation of analgesia. These data indicate that the aforementioned brain regions and neurotransmitters such as endogenous opioid and dopamine systems contribute to placebo analgesia.