Placebo analgesia: findings from brain imaging studies and emerging hypotheses

Placebo analgesia is one of the most robust and best-studied placebo effects. With the help of brain imaging tools, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), our understanding of the brain's role in placebo analgesia has been greatly expanded. Previous studies suggest that multiple mechanisms may underlie the phenomenon of placebo analgesia. This review posits a theoretical framework for interpreting the results of the neuroimaging literature of placebo analgesia. According to this framework, placebo treatment may exert an analgesic effect on at least three stages of pain processing, by 1) influencing pre-stimulus expectation of pain relief, 2) modifying pain perception, and 3) distorting post-stimulus pain rating. Importantly, change in one such stage may hasten change in another, and furthermore, contribution from any or all of the three stages may vary by circumstance, or between individuals. The literature suggests that multiple brain regions, including the anterior cingulate cortex, anterior insula, prefrontal cortex and periaqueductal grey, play a pivotal role in these processes.