|| Checking for direct PDF access through Ovid
Patients in randomized clinical trials frequently stop taking their drug, complaining of side effects. However, it turns out that some of these subjects are part of the placebo group and thus never received any active medication. This is a case of the nocebo effect seriously interfering with medical treatment. Tinnermann et al. investigated whether value information such as the price of a medication can further modulate behavioral nocebo effects and the underlying neural network dynamics (see the Perspective by Colloca). They used brain imaging to characterize the circuits involved in nocebo hyperalgesia within the descending pain pathway from the prefrontal cortex to the spinal cord. Their findings revealed how value information increased the nocebo effect.Science, this issue p. 105; see also p. 44Value information about a drug, such as the price tag, can strongly affect its therapeutic effect. We discovered that value information influences adverse treatment outcomes in humans even in the absence of an active substance. Labeling an inert treatment as expensive medication led to stronger nocebo hyperalgesia than labeling it as cheap medication. This effect was mediated by neural interactions between cortex, brainstem, and spinal cord. In particular, activity in the prefrontal cortex mediated the effect of value on nocebo hyperalgesia. Value furthermore modulated coupling between prefrontal areas, brainstem, and spinal cord, which might represent a flexible mechanism through which higher-cognitive representations, such as value, can modulate early pain processing.