Anticipation and Placebo Analgesia

  • Dominic E. Nathan
  • Taylor M. Ludman
  • Luana Colloca


The neural substrates of the anticipatory phase of an impending stimulus have been studied in the context of pain with neuromapping techniques, including both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The neural response during the anticipatory phase is complex since it can be affected by many factors, including certainty and uncertainty, dispositional anxiety and pathology, which have been the topic of many past studies. Importantly, the anticipation of pain is affected by positive and negative expectancies , namely the placebo and nocebo phenomena which serve as great examples of how expectancies created during the anticipatory phase can modulate pain perception. Here we critically discuss the literature on the neural activity throughout the anticipatory phase preceding a noxious stimulus and during the delivery of a stimulus when placebo and nocebo effects modulate pain. Understanding the processes during the anticipatory phase and the placebo and nocebo effects can help increase knowledge of both acute and chronic pain mechanisms, identify biological predictors of variability in clinical pain phenotypes and ultimately contribute to new therapeutic approaches.


Anticipation Expectancies Placebo Nocebo Brain imaging 





Anterior cingulate cortex

rACC, sACC or pgACC (respectively)

Rostral or subgenual or pregenual ACC


Insular cortex


Midcingulate cortex


Nucleus accumbens


Orbitofrontal cortex


Periaqueductal gray


Prefrontal cortex


Dorsolateral prefrontal cortex


Ventral medial prefrontal cortex


Primary somatosensory cortex


Rostral ventral medulla




Ventral tegmental area



This project was supported by University of Maryland Baltimore (LC), the National Institute of Dental and Craniofacial Research (NIDCR; R01DE025946-01, LC) and International Association for Study of Pain (Early Research Grant [LC]).


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Dominic E. Nathan
    • 1
  • Taylor M. Ludman
    • 2
    • 3
  • Luana Colloca
    • 2
    • 3
    • 4
  1. 1.Uniformed Services University of the Health Sciences, School of NursingBethesdaUSA
  2. 2.Pain and Translational Symptom ScienceUniversity of Maryland Baltimore, School of NursingBaltimoreUSA
  3. 3.UM Center to Advance Chronic Pain ResearchBaltimoreUSA
  4. 4.Department of AnesthesiologyUniversity of Maryland Baltimore, School of MedicineBaltimoreUSA

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