People often feel better when they believe they have taken a painkiller—even if its a placebo. Now, researchers at the University of Michigan and the University of Maryland have shown that the placebo effect is not merely psychological and that it has a physiological basis (J. Neurosci. 2005, 25, 7754). Michigans Jon-Kar Zubieta and colleagues injected saline solution into the jaw muscles of male volunteers to cause pain. As the experiment proceeded, additional solution was administered to the men at a rate that kept their perceived pain constant. The men were told they would also be injected with either a placebo or a compound that could reduce the pain; unbeknownst to the volunteers, only a placebo was used. The researchers used positron emission tomography and magnetic resonance imaging to scan the mens brains for activity in regions that release the natural opiates known as endorphins. The scans showed that administration of the placebo was followed by increased endorphin activity, providing the men with increased pain resistance.