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.