Novel designs and paradigms to study the placebo response in gastroenterology.

The investigation of the placebo and the nocebo effect and their mechanisms has a rather short history of less than 20 years, especially in gastroenterology, and only the last 5 years have resulted in substantial improvement of understanding. Placebo refers to symptom improvement following a treatment, nocebo to the opposite, symptom worsening. Among the factors driving this progress are traditional psychological models derived from learning (conditioning) theory bridging into clinical science, new animal models to investigate the pharmacology of placebo analgesia, and novel study designs to overcome limitations of traditional randomized and placebo-controlled study designs in drug testing. These are explored here for their implementation and application in gastroenterology, with a focus on visceral pain and nausea.