In the 1950s, Henry Beecher, the Harvard pioneer of pain studies already mentioned, and his colleague Lasagna studied a placebo versus morphine for the treatment of postoperative pain. Each patient received two medications, morphine and a placebo, but the order of the two was varied. Half the patients received the placebo first and half received the morphine first. They found that those who received the morphine first responded very well to the second injection, which was a placebo. By contrast, those who received the placebo first responded rather poorly to the second injection, which was morphine. Evidently, the patients’ expectation had been built up by their experience of the first trial.
Fifty years later, this crucial and surprising effect is still studied in Turin by Fabrizio Benedetti’s team. They were treating 33 patients who had been operated on for the removal of part of one lung, a famously painful type of surgery. The patients were treated for their pain for twelve to eighteen hours after their operation with intravenous buprenorphine, a powerful narcotic. Their pain was carefully monitored during this time, as was their lung function. One of the side effects of narcotics is to depress respiration, although the patients were quite unaware of this effect.
As shown long ago by Beecher and Lasagna, the pain responses to narcotics is surprisingly variable. Some patients achieve excellent pain relief with one small dose while others require repeated doses to get the same reduction of pain. The same applies to the side effects. After the Turin patients had experienced satisfactory narcotic-induced pain relief for twelve to eighteen hours, each was given placebo injections of saline. The results show clearly that those patients who responded to small doses of the narcotics also responded well to small doses of the placebo. Even more surprisingly, those patients who, unknown to them, responded with respiratory depression to the narcotics, also showed respiratory depression with the placebo. Evidently, the placebo mimics the details of the experienced pain relief and the covert side effects. It is apparent that the placebo may be indistinguishable from the drug after the patient had experienced the drug’s effect.
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