Fig. 3

Neurophysiological mechanisms of placebo, nocebo and context-related effects. Principal neurobiological mechanisms of placebo, nocebo and context related effects. a Pharmacological studies. The opioid and cannabinoid systems are involved in placebo and nocebo effects. In some circumstances, placebo analgesia occurs through the activation of the opioid system and can be reversed by naloxone. In other circumstances, placebo analgesia occurs through the activation of the cannabinoid system and can be reversed by rimonabant. Anticipatory anxiety can activate the pro-nociceptive cholecystokinin (CCK) system, leading to nocebo hyperalgesia. The pro-nociceptive CCK effect can be reversed by proglumide and agonized by pentagastrin. b Neuroimaging studies. The activation and deactivation of different brain regions during placebo analgesia and nocebo hyperalgesia have been described trough different brain imaging studies. c Electrophysiological studies. Electroencephalographic (EEG) studies showed the dynamical studies showed the dynamical and temporal changes that occur in the brain before and after the administration of inert treatments