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

Abstract

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.

Placebo analgesia affects the behavioral despair tests and hormonal secretions in mice

“…The question whether the placebo effect depends more on classical conditioning or on cognitive processes was directly examined in several studies (Benedetti et al 2003a, b;Price et al 1999). Conditioning theorists have proposed that the placebo is a conditioned Pavlovian response, whereas others have advocated that the placebo is driven by expectancy (Kirsch 2004;Klinger et al 2007;Rescorla 1988;Stewart-Williams and Podd 2004;Wager and Nitschke 2005). The placebo analgesia effect investigated in this study might be brought about mainly through expectation.…”

How placebo responses are formed: a learning perspective

“…They showed that conditioning supports the maintenance of placebo responses in a patient population. Additionally, the authors demonstrated that the patient's history plays an important role in the formation of placebo responses [53]. Patients have a completely different history of exposure to medications and healing experiences, suggesting that the prior experience of those who interpret placebos as sign vehicles have differential impacts on the formation of placebo responses.…”

There’s More to Placebo-Related Improvement Than the Placebo Effect Alone

“…For example, in patients with pain, placebo mechanisms may involve the release of endogenous opioids 2 and endogenous cannabinoids 3 ; in patients with Parkinson's disease, placebo mechanisms may involve the release of dopamine. 1 Such mechanisms, in turn, may depend on expectancy and classical conditioning 4 ; after all, if the sound of a bell can trigger salivation or if the sight of food can stimulate the secretion of gastric juices, then perhaps the sight of a doctor's office, the swallowing of a colored pill, or the prick of a syringe may trigger the release of the appropriate chemicals for the relief of pain, anxiety, or depression. Nevertheless, what the placebo mechanism is in complex psychiatric disorders is poorly understood.…”