Brain mechanisms supporting violated expectations of pain

Abstract

The subjective experience of pain is influenced by interactions between prior experiences, future predictions and incoming afferent information. Expectations of high pain can exacerbate pain while 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 in order to override erroneous top-down expectancy-mediated information. The present investigation examined pain-related brain activation when expectations of pain were abruptly violated. After conditioning participants to cues predicting low or high pain, ten incorrectly cued stimuli were administered across 56 stimulus trials to determine if expectations would be less influential on pain when there is a high discordance between pre-stimulus 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 where patients’ unrealistic expectations for 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.

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia

“…We predicted that placebo analgesia would be associated with decreased painrelated brain activation and dorsolateral prefrontal cortex (DLPFC) activation, a brain region critically involved in placebo and maintaining contextual expectations for pain relief (Wager et al, 2004;Eippert et al, 2009;Lui et al, 2010;Petrovic et al, 2010;Atlas et al, 2012;Geuter et al, 2013). In contrast, we predicted that mindfulness-based pain relief would be associated with greater activation in sensory processing regions such as the secondary somatosensory cortex (SII) and insula (Grant et al, 2010;Gard et al, 2012;Zeidan et al, 2011) and higher-order brain regions such as the orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) (Hölzel et al, 2011;Zeidan et al, 2011;Zeidan et al, 2012).…”

“…As described previously (Koyama et al, 2005;Oshiro et al, 2007;Quevedo andCoghill, 2007a,b, 2009;Starr et al, 2009;Yelle et al, 2009;Zeidan et al, 2011;Lobanov et al, 2013;Lobanov et al, 2014;Zeidan et al, 2015), a TSA-II device (Medoc) was used to deliver all thermal stimuli using a 16 mm 2 surface area thermal probe. This modest stimulus area There were no significant differences between groups on age and gender.…”

“…We therefore compared active mindfulness meditation with a validated sham mindfulness meditation technique (Zeidan et al, 2010b). Although the behavioral and neural mechanisms associated with sham mindfulness meditation are not known, it was hypothesized that sham mindfulness meditation would reduce pain by engaging mechanisms more aligned with placebo analgesia (i.e., DLPFC; Wager and Atlas, 2015) and relaxation (i.e., decreased respiration rate; Beary and Benson, 1974).…”

“…Despite the commonly held assumption that mindfulness meditation shares much in common with other placebo manipulations, the neural mechanisms supporting mindfulness-based pain relief have yet to be compared with those engaged by placebo analgesia (Salomons and Kucyi, 2011;Zeidan et al, 2012). Accordingly, the present longitudinal study combined psychophysical, physiological, and pseudocontinuous arterial spin-labeled MRI (PCASL) methodologies in pain-free, healthy volunteers to test the hypothesis that mindfulness meditation produces greater pain reductions and activates distinct neural mechanisms from those engaged by placebo analgesia.…”

“…The analgesic effects of meditation could also be driven by the nonspecific components of participating in a meditation intervention. Such components would include psychosocial contexts, facilitator attention, intervention setting, body posture, and/or demand characteristics associated with the belief that one is practicing meditation (Salomons and Kucyi, 2011;Zeidan et al, 2012;Tang et al, 2015).…”