Pain experience: lessons from placebo and nocebo studies

A placebo response is a psychological and biological phenomenon occurring in the patient’s brain following the administration of an inert substance or of a sham physical treatment, along with verbal suggestions, or any other cue, of clinical benefit. The effect that follows the administration of a placebo is not due to the inert treatment per se, for saline solutions or sugar pills will never acquire therapeutic properties, but to the psychosocial context that surrounds the inert substance and the patient. In this sense, to the clinical trialist and to the neurobiologist, the term “placebo effect” or “placebo response” has different meanings. The former is interested in any improvement that may occur in the group of patients who receive the inert treatment, regardless of its cause, because he only wants to establish whether the patients who take the true treatment are better off than those who take the placebo, irrespective of whether such observed improvement is due to spontaneous remission of the disease, doctor’s biases in selecting patients, and patient’s biases in reporting symptoms. By contrast, the psychologist and the neuroscientist are only interested in the improvement that derives from active processes occurring in the patient’s brain, such as the patient’s expectations of clinical improvement. The same concepts hold true for the nocebo response, a phenomenon that is opposite to the placebo response, whereby an inert treatment is administered along with negative verbal suggestions of worsening. Taking these considerations into account, the placebo and nocebo are not the inert treatments alone, but rather their administration within a set of sensory and social stimuli that tell the patient that either a beneficial or a harmful treatment, respectively, is being given.

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