Classical conditioning and expectancy in placebo hypoalgesia: a randomized controlled study in patients with atopic dermatitis and persons with healthy skin

Pain. 2007 Mar;128(1-2):31-9. doi: 10.1016/j.pain.2006.08.025. Epub 2006 Oct 9.


The effectiveness of placebos is unchallenged. However, it is still not clear on which mechanisms the placebo effect is based. Besides expectancy theories, classical conditioning is discussed as a major explanatory model. In an experimental conditioning design we tested 96 participants, 48 with atopic dermatitis (24 male, 24 female) and 48 with healthy skin (24 male and 24 female). All of them received a neutral ointment with a different briefing ("pain-reducing ointment" versus "neutral ointment"). Electrical pain stimuli were subsequently applied, which selectively induce a painful sensation. In the case of the learning condition (classical conditioning) and unbeknown to the participants, the intensity of the pain stimulus was reduced by 50% after the ointment had been applied. The study addressed the question whether the pain experienced by the patients with atopic dermatitis could be reduced through a placebo effect and whether the placebo effect was achieved through expectancy or through a process of classical conditioning or both. The results indicate that a placebo effect is achieved via expectancy and classical conditioning. However, conditioning processes seem to be necessary for a longer lasting effect. The extent of this effect seemed to be greater in atopics than in healthy controls. Expectancy, achieved through verbal instruction, might also be seen as a conditioned stimulus that reactivates earlier stimulus associations.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Cognition / drug effects
  • Conditioning, Classical / drug effects*
  • Dermatitis, Atopic / complications
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / psychology*
  • Dermatologic Agents / administration & dosage
  • Female
  • Humans
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Hyperalgesia / psychology*
  • Male
  • Models, Psychological
  • Pain Threshold / drug effects*
  • Placebo Effect*
  • Treatment Outcome


  • Dermatologic Agents