Distinct neural networks subserve placebo analgesia and nocebo hyperalgesia

Neuroimage. 2021 May 1:231:117833. doi: 10.1016/j.neuroimage.2021.117833. Epub 2021 Feb 5.


Neural networks involved in placebo analgesia and nocebo hyperalgesia processes have been widely investigated with neuroimaging methods. However, few studies have directly compared these two processes and it remains unclear whether common or distinct neural circuits are involved. To address this issue, we implemented a coordinate-based meta-analysis and compared neural representations of placebo analgesia (30 studies; 205 foci; 677 subjects) and nocebo hyperalgesia (22 studies; 301 foci; 401 subjects). Contrast analyses confirmed placebo-specific concordance in the right ventral striatum, and nocebo-specific concordance in the dorsal anterior cingulate cortex (dACC), left posterior insula and left parietal operculum during combined pain anticipation and administration stages. Importantly, no overlapping regions were found for these two processes in conjunction analyses, even when the threshold was low. Meta-analytic connectivity modeling (MACM) and resting-state functional connectivity (RSFC) analyses on key regions further confirmed the distinct brain networks underlying placebo analgesia and nocebo hyperalgesia. Together, these findings indicate that the placebo analgesia and nocebo hyperalgesia processes involve distinct neural circuits, which supports the view that the two phenomena may operate via different neuropsychological processes.

Keywords: Activation likelihood estimation; Functional decoding; Meta-analysis; Meta-analytic connectivity modeling; Nocebo hyperalgesia; Placebo analgesia; Resting-state functional connectivity.

Publication types

  • Meta-Analysis

MeSH terms

  • Analgesia / methods*
  • Brain / diagnostic imaging*
  • Brain / physiopathology
  • Brain Mapping / methods
  • Humans
  • Hyperalgesia / diagnostic imaging*
  • Hyperalgesia / physiopathology
  • Hyperalgesia / therapy
  • Magnetic Resonance Imaging / methods
  • Nerve Net / diagnostic imaging*
  • Nerve Net / physiopathology
  • Nocebo Effect
  • Pain / diagnostic imaging*
  • Pain / physiopathology
  • Placebo Effect
  • Positron-Emission Tomography / methods