[Placebo effect and pain: brain bases]

All pharmacological treatment is surrounded by a psychosocial context that contributes in part to the outcome of the therapy. The placebo effect is the improvement observed after a simulated treatment in which the subject, without his or her knowledge, is exposed only to the psychosocial context surrounding the treatment, without receiving the pure "pharmacodynamic" effect of the medication. The aim of this paper is to examine which brain regions and neurochemical mechanisms are responsible for the analgesia resulting from the placebo.

Recent studies using functional neuroimaging methods have suggested that when expectations of analgesia arise because of a simulated treatment (placebo) there is an increase in the activity of the dorsolateral and orbitofrontal prefrontal cortices. These increments are detected early on, before the experience of pain, which suggests that these structures could be part of a system that is involved in the cognitive control of pain. Several studies have found that once the subject experiences the nociceptive stimulus, the placebo causes a significant reduction in the activity of cortical regions classically associated with nociceptive processing, mainly the anterior insula and the rostral cingulate. In these regions the attenuation of the pain processing seems to be mediated by the release of opioids.

In placebo analgesia at least two anatomically differentiated cerebral systems work together. The guiding mechanism, which appears to be located prefrontally, is activated first. This system would influence other cortical regions (cingulate and insula), attenuating the processing of nociceptive information at these higher levels.