Patients in randomized clinical trials frequently stop taking their drug, complaining of side effects. Often, it turns out that 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. We investigated the mechanism of nocebo hyperalgesia from a network perspective (top) and whether value (i.e. price tag) can modulate its magnitude. Using an in-house developed novel brain-spinal cord fMRI protocol we could show the involvement of the descending pain pathway from the prefrontal cortex over the PAG to the spinal cord. In addition, we could show that a more expensive placebo leads to a greater placebo effect (bottom) paralleled by a greater activation of the rACC.
Placebo hypoalgesia (top) and nocebo hyperalgesia (middle) are prime examples of the impact that psychological factors have on pain perception. Using functional magnetic resonance imaging of the human spinal cord we could show that placebo analgesia results in a reduction of nociceptive processing (top), whereas nocebo hyperalgesia results in an increase of activation in the spinal cord (middle). Similar to placebo hypoalgesia, we observed a reduction of activation in the spinal cord during a demanding cognitive task (2-back working memory). Both cognitive distraction and placebo hypoalgesia are mediated by endogenous opioids. The mechanism of nocebo hyperalgesia is still unclear.
We put forward the idea that the brain is not passively waiting for nociceptive stimuli to impinge on it but is actively making inferences based on prior experience and expectations (top). The Bayesian formulation within the predictive coding framework can directly account for differences in the magnitude but also the precision of expectations that are known to influence the strength of placebo hypoalgesia. We then experimentally tested these hypotheses and could show (middle) that decreasing the precision of expectations reduces placebo hjypolagesia. Finally, a cued pain paradigm indicated that posterior areas in the insula region such as S2 simply code pain intensity (blue), whereas anterior regions (yellow) represent predictions and prediction errors regarding pain.
Our work horse for many imaging studies. This is also the sanner on which we perform spinal cord fMRI and combined cortico-spinal fMRI.
During fMRI we acquire many additional bio signals including heartrate, eye-movemnts, pupil diameter, skin conducatnce. Stimulation during fMRI can be done
The Department runs many labs for behavioral assessments. These include a large lab for groups, e.g. to study social interactions, dedicated labs for eye-tracking and labs for pain application including pharmacological challenges.
Self explaining.
Fun fact: This is the place where the idea for the combined cortico-spinal cord fMRI protocol was born (together with Jürgen Finsterbusch).