The Role of Tactile Stimulation for Expectation, Perceived Treatment Assignment and the Placebo Effect in an Experimental Nausea Paradigm

The power of placebos has long been recognized for improving numerous medical conditions such as Parkinson's disease (PD). Little is known, however, about the mechanism underlying the placebo effect. Using the ability of endogenous dopamine to compete for [11C]raclopride binding as measured by positron emission tomography, we provide in vivo evidence for substantial release of endogenous dopamine in the striatum of PD patients in response to placebo. Our findings indicate that the placebo effect in PD is powerful and is mediated through activation of the damaged nigrostriatal dopamine system.

In a pooled analysis of four randomized controlled trials of acupuncture in patients with migraine, tension-type headache, chronic low back pain, and osteoarthritis of the knee we investigated the influence of expectations on clinical outcome. The 864 patients included in the analysis received either 12 sessions of acupuncture or minimal (i.e. sham) acupuncture (superficial needling of non-acupuncture points) over an 8 week period. Patients were asked at baseline whether they considered acupuncture to be an effective therapy in general and what they personally expected from the treatment. After three acupuncture sessions patients were asked how confident they were that they would benefit from the treatment strategy they were receiving. Patients were classified as responders if the respective main outcome measure improved by at least fifty percent. Both univariate and multivariate analyses adjusted for potential confounders (such as condition, intervention group, age, sex, duration of complaints, etc.) consistently showed a significant influence of attitudes and expectations on outcome. After completion of treatment, the odds ratio for response between patients considering acupuncture an effective or highly effective therapy and patients who were more sceptical was 1.67 (95% confidence interval 1.20-2.32). For personal expectations and confidence after the third session, odds ratios were 2.03 (1.26-3.26) and 2.35 (1.68-3.30), respectively. Results from the 6-month follow-up were similar. In conclusion, in our trials a significant association was shown between better improvement and higher outcome expectations.

Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical conceptualization of the placebo effect remains poorly developed. Substantial mechanistic research on this phenomenon has proceeded with little guidance by any systematic theoretical paradigm. This review seeks to present a theoretical perspective on the formation of placebo responses. We focus on information processing, and argue that different kinds of learning along with individuals' genetic make-up evolved as the proximate cause for triggering behavioural and neural mechanisms that enable the formation of individual expectations and placebo responses. Conceptualizing the placebo effect in terms of learning offers the opportunity for facilitating scientific investigation with a significant impact on medical care.