Secondary Logo

Institutional members access full text with Ovid®

Brain mechanisms supporting violated expectations of pain

Zeidan, Fadela; Lobanov, Oleg V.a; Kraft, Robert A.b; Coghill, Robert C.a,*

doi: 10.1097/j.pain.0000000000000231
Research Paper
Editor's Choice

The subjective experience of pain is influenced by interactions between experiences, future predictions, and incoming afferent information. Expectations of high pain can exacerbate pain, whereas expectations of low pain during a consistently noxious stimulus can produce significant reductions in pain. However, the brain mechanisms associated with processing mismatches between expected and experienced pain are poorly understood, but are important for imparting salience to a sensory event to override erroneous top–down expectancy-mediated information. This investigation examined pain-related brain activation when expectations of pain were abruptly violated. After conditioning participants to cues predicting low or high pain, 10 incorrectly cued stimuli were administered across 56 stimulus trials to determine whether expectations would be less influential on pain when there is a high discordance between prestimulus cues and corresponding thermal stimulation. Incorrectly cued stimuli produced pain ratings and pain-related brain activation consistent with placebo analgesia, nocebo hyperalgesia, and violated expectations. Violated expectations of pain were associated with activation in distinct regions of the inferior parietal lobe, including the supramarginal and angular gyrus, and intraparietal sulcus, the superior parietal lobe, cerebellum, and occipital lobe. Thus, violated expectations of pain engage mechanisms supporting salience-driven sensory discrimination, working memory, and associative learning processes. By overriding the influence of expectations on pain, these brain mechanisms are likely engaged in clinical situations in which patients' unrealistic expectations of pain relief diminish the efficacy of pain treatments. Accordingly, these findings underscore the importance of maintaining realistic expectations to augment the effectiveness of pain management.

Supplemental Digital Content is Available in the Text.The left posterior parietal cortex is activated when expectations of an impending noxious stimulus are violated by a large discrepancy between expected and experienced pain.

Departments ofaNeurobiology and Anatomy

bBiomedical Engineering, Wake Forest School of Medicine, Winston-Salem, NC, USA

Corresponding author. Address: Department of Neurobiology and Anatomy, Wake Forest School of Medicine, Winston-Salem, NC 27157-1010, USA. Tel.: +1 336 716 4284; fax: +1 336 716 4534. E-mail address: (R. C. Coghill).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received February 24, 2015

Received in revised form May 05, 2015

Accepted May 06, 2015

© 2015 International Association for the Study of Pain
You currently do not have access to this article

To access this article:

Note: If your society membership provides full-access, you may need to login on your society website