Different contexts, different pains, different experiences.

Pain is an ambiguous perception: the same pain stimulation can be perceived differently in different contexts, producing different experiences, ranging from mild to unbearable pain. It can be even experienced as a rewarding sensation within the appropriate context. Overall, placebo and nocebo effects appear to be very good models to understand how the psychosocial context modulates the experience of pain. In this review, we examine the effects of different contexts on pain, with a specific focus on the neurobiological mechanisms. Positive and rewarding contexts inform the patients that an effective treatment is being delivered and are capable of producing pain relief through the activation of specific systems such as opioids, cannabinoids and dopamine. Conversely, a negative context can produce pain exacerbation and clinical worsening through the modulation of different systems, such as the activation of cholecystokinin and the deactivation of opioids and dopamine. In addition, when a therapy is delivered unbeknownst to the patient, its effects are reduced. A better understanding of the neurobiological underpinnings of the context-pain interaction is a challenge both for future pain research and for good clinical practice.