ArticlesBlockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumideBenedetti, Fabrizioa,b,*; Amanzio, Martinaa,b; Casadio, Caterinac; Oliaro, Albertoc; Maggi, GiulianocAuthor Information aDipartimento di Neuroscienze, Università di Torino, Corso Raffaello 30, 10125 Torino, Italy bCIND Center for the Neurophysiology of Pain, University of Torino Medical School, Torino, Italy cDepartment of Thoracic Surgery, University of Torino Medical School, Torino, Italy *Corresponding author. Tel.: +39 11 670 77 09; fax: +39 11 670 77 08. Received October 28, 1996; revised version received January 8, 1997; accepted January 15, 1997. Pain: June 1997 - Volume 71 - Issue 2 - p 135-140 doi: 10.1016/S0304-3959(97)03346-0 Buy Metrics Abstract In patients who reported mild postoperative pain, we evoked a nocebo response, a phenomenon equal but opposite to placebo. Patients who gave informed consent to increase their pain for 30 min received a substance known to be non–hyperalgesic (saline solution) and were told that it produced a pain increase. A nocebo effect was observed when saline was administered. However, if a dose of 0.5 or 5 mg of the cholecystokinin antagonist proglumide was added to the saline solution, the nocebo effect was abolished. A dose of 0.05 mg of proglumide was ineffective. The blockade of the nocebo hyperalgesic response was not reversed by 10 mg of naloxone. These results suggest that cholecystokinin mediates pain increase in the nocebo response and that proglumide blocks nocebo through mechanisms not involving opioids. Since the nocebo procedure represents an anxiogenic stimulus and previous studies showed a role for cholecystokinin in anxiety, we suggest that nocebo hyperalgesia may be due to a cholecystokinin-dependent increase of anxiety. © Lippincott-Raven Publishers.