A Monthly Critical Overview of Current Medicine

Placebo Analgesia: When and How It Works A s neurophysiologists have demonstrated experimentally, placebo analgesia is mediated by endogenous opioids. In clinical trials comparing placebo with no treatment, the placebo had no effect on pain management. But the placebo response may depend on psychological factors such as conditioning, expectancy, and the method of analgesic assessment, and these psychological influences may act via endogenous opioids. To explore response expectancies as determinants of placebo analgesia, neuroscientists at Italy's University of Torino assigned 38 thoracotomized patients to three groups. All were treated with the opioid buprenorphine on request, together with a basal infusion of saline solution. Group 1 (natural history) was told nothing about any analgesic effect the basal infusion might provide. Group 2 (classic double-blind administration) was told that the basal infusion would be either a powerful painkiller or a placebo. Group 3 (deceptive administration) was told the basal infusion was a potent painkiller. Analgesia was assessed by the amount of buprenorphine requested during the three-day study period. Compared with the natural-history group, the double-blind group showed a reduction in buprenorphine requests. In the deceptive-administration group, the reduction was even greater. In an earlier report by the same team, the analgesia of the opioids buprenorphine and tramadol and the nonopioids ketorolac and metamizole was greater when the drugs were administered by injection, in full view of the subject instead of in hidden infusions. In a second part of the study, experimental ischemic arm pain induced in healthy volunteers was reduced more effectively by open than hidden administration of ketorolac. Adding naloxone to the injections produced a pharmacologic block of the endogenousopioid-mediated component of placebo analgesia.