Classically conditioned modulation of pain depends on stimulus intensity

Daniel S. Harvie, Eva Y. Poolman, Victoria J. Madden, Nick A. Olthof, Michel W. Coppieters*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Innocuous cues that become associated with pain can enhance pain. This is termed classically conditioned hyperalgesia. The size of this effect varies under different conditions. We aimed to test whether the sensitising effect of pain-associated cues depends on the intensity of the paired test stimulus. To do this, two virtual reality environments were paired with either painful or non-painful vibrotactile stimuli in a counterbalanced fashion. The differential effect of the two environments was evaluated using pain intensity ratings of paired electrocutaneous test stimuli at three different intensity levels. Forty healthy participants were included in the study; 30 participants experienced sufficient pain during the learning phase and were included in the main analysis. An effect of environment (p = 0.014) and interaction between environment and test stimulus intensity was found (p = 0.046). Only the most intense test stimulus was modulated by environment. While the effect was small, the results are consistent with the proposition that pain-associated cues may induce hyperalgesia to some degree, under certain conditions. In particular, results highlight the potential relevance of stimulus intensity during and after the initial painful experience. Further attention is needed to comprehensively understand the variables that impact classically conditioned hyperalgesia.

Original languageEnglish
Pages (from-to)1151-1158
Number of pages8
JournalExperimental Brain Research
Issue number4
Early online date11 Feb 2022
Publication statusPublished - Apr 2022

Bibliographical note

Funding Information:
DH is supported by an Early Career Research Fellowship from the National Health and Medical Research Council of Australia (GNT1142929). VJM is supported by the Fogarty International Center of the National Institutes of Health (award K43TW011442). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
The authors would like to thank Associate Professor Ross Smith (Wearable Computer Lab, University of South Australia) for creating the Virtual Reality software that enabled simple display of, and interchange between, the scenes.

Publisher Copyright:
© 2022, The Author(s).


  • Associative learning
  • Chronic pain
  • Classical conditioning
  • Conditioned hyperalgesia
  • Nocebo
  • Psychophysics


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