**7.14 Placebo effect**

One relevant aspect not sufficiently discussed is the placebo effect, which can be sometimes one of the most important pieces of the treatment. Conceptualization of the placebo phenomenon has significantly changed during the last decades and this armamentarium is now intended as related to the patient's perception of a treatment. Of course, this is directly related to the patient's previous experience and the patient-practitioner relationship and confidence as well as with expectations, emotions, and beliefs. However, all those factors impact on cerebral function and release of endogenous opioids. Moreover, the placebo effect has a psycho-neurobiological base, since brain image studies performed in healthy volunteers show increased cortical activity particularly in the dorsolateral prefrontal cortex and orbitofrontal cortex, possibly associated with expectations of pain relief. On the other hand, the placebo analgesia is related to decrease of the neural activity in structures like thalamus, insula, and the anterior cingulate cortex, which constitute the so-called pain matrix [97]. The endogenous opioid system is probably involved in the placebo analgesia mechanism since opioid antagonists were shown to block the placebo effect [98]. Interestingly, the placebo mechanism was shown also to interfere with insomnia, even when patients did know they were taking a pharmacologically inactive substance [99]. It is of crucial importance for clinicians to be aware of how the placebo components may affect (enhance or reduce) the outcome of active treatment in chronic pain patients in order to separate either the therapeutic effect from the placebo one and to optimize treatment outcome.
