Endogenous opioids in placebo-induced analgesia

Placebos achieve scientifically proven pain-relieving effects yet are inactive substances for the treatment of pain. Levine, Gordon, and Fields were the first to demonstrate the role of endogenous opioids in placebo-induced analgesia during dental post-operative pain. Several studies using pharmacological manipulations and/or neuroimaging techniques confirmed their findings that placebo analgesia is reversible by naloxone, and also identified brain pathways involved in opioidergic neurotransmission during placebo analgesia (prefrontal regions rich in opioid receptors such as the anterior cingulate cortex, presumably initiating descending pain modulation through downstream projections to the brainstem). Fifty years of research in pharmacology and neurobiology have contributed to the identification of physical as well as psychological determinants of placebo analgesia. Expectations of pain relief are maintained by conditioned learning and reward-related processes, reflected by interactions between different neurotransmitters (opioids, dopamine, endocannabinoids) in a variety of brain circuits related to executive/cognitive processes as well as affect and reward.