Placebo analgesia is a kind of pain relief that follows the administration of a pharmacologically inert treatment and is thought to result from the activation of endogenous pain modulatory system by psychological processes such as expectation and implication. Neuroimaging studies in humans have suggested that the hierarchical brain regions and neurochemical systems, such as endogenous opioid system, are involved in the placebo analgesia. However, because of the lack of proper approaches to perform molecular and cellular manipulations, the detailed molecular processes behind it have not been clarified. Recently, we have developed a small-animal neuroimaging method that combines FDG-PET imaging with SPM analysis for investigating regional brain activity in the entire rat brain. Using this method, we have identified that widely distributed brain regions, which are quite similar to those of human neuroimaging studies could be involved in Pavlovian conditioning-induced placebo analgesia, and demonstrated that the endogenous µ opioid system in the PrL, causally contributed to placebo analgesia in rats. In this symposium, I will introduce the neurobiological mechanism of placebo analgesia how the endogenous opioid system activates the descending pain modulatory pathway.