The periaqueductal gray and Bayesian integration in placebo analgesia

Elife. 2018 Mar 20;7:e32930. doi: 10.7554/eLife.32930.


In placebo hypoalgesia research, the strength of treatment expectations and experiences are key components. However, the reliability or precision of expectations had been mostly ignored although being a likely source for interindividual differences. In the present study, we adopted a Bayesian framework, naturally combining expectation magnitudes and precisions. This postulates that expectations (prior) are integrated with incoming nociceptive information (likelihood) and both are weighted by their relative precision to form the pain percept and placebo effect. Sixty-two healthy subjects received heat pain during fMRI. Placebo effects were more pronounced in subjects with more precise treatment expectations and correlated positively with the relative precision of the prior expectation. Neural correlates of this precision were observed in the periaqueductal gray and the rostral ventromedial medulla, indicating that already at the level of the brainstem the precision of an expectation can influence pain perception presenting strong evidence for Bayesian integration in placebo hypoalgesia.

Keywords: Bayesian; PAG; computational biology; fMRI; human; neuroscience; pain; placebo analgesia; precision; systems biology.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Analgesia / methods
  • Bayes Theorem*
  • Brain Mapping
  • Double-Blind Method
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Medulla Oblongata / diagnostic imaging
  • Medulla Oblongata / physiopathology
  • Models, Neurological
  • Pain / diagnosis
  • Pain / diagnostic imaging
  • Pain / physiopathology*
  • Pain Perception / physiology*
  • Periaqueductal Gray / diagnostic imaging
  • Periaqueductal Gray / physiopathology*
  • Placebo Effect*
  • Young Adult