Mechanism of placebo analgesia
Several years ago it was reported that the opiate antagonist naloxone can reverse the analgesia produced by a placebo. This led to the hypothesis that placebo analgesia involves release of endorphins and activation of an endogenous pain control circuit. This striking finding has received considerable support in recent studies in which regulators of endorphin processing have been shown to enhance the effect of a placebo. The new studies followed upon basic experimental evidence that the neuropeptide cholecystokinin (CCK) counteracts the effect of endogenous opioids. The new studies demonstrated that injection of a CCK receptor antagonist significantly increased the analgesic effect of a placebo. Furthermore, the enhancing effect of the original placebo effect were both blocked by naloxone, indicating that the circuit involves release of endogenous opioids, which act at opioid receptors. Recent imaging studies demonstrated that placebo analgesia is associated with activation of areas involved in the endorphin-mediated descending control of pain processing (e.g., the periaqueductal gray region of the midbrain).