OBJECTIVE: Expectations contribute to cognitive pain modulation through opioidergically mediated descending inhibition. Mindfulness meditation reduces pain independent of endogenous opioids, engaging unique corticothalamocortical mechanisms. However, it remains unknown whether expectations for pain relief predict mindfulness-induced analgesia and if these expectations are modified by endogenous opioids. METHODS: In this secondary analysis of previously published work, 78 pain-free participants (mean age, 27 ± 7 years; 50% women) were randomized to a four-session mindfulness meditation or book listening regimen. Expectations for intervention-induced pain relief were assessed before and after each intervention. Pain ratings were examined after meditation or rest (control group) during noxious heat (49°C) and intravenous administration of saline placebo or the opioid antagonist naloxone (0.15 mg/kg bolus + 0.1 mg kg-1 h-1 infusion. RESULTS: Mindfulness significantly lowered pain during saline and naloxone infusion. Higher expected pain relief from mindfulness predicted lower pain intensity (r(40) = -0.41, p = .009). The relationship between meditation-related expectations and pain intensity reductions was exhibited during naloxone (r(20) = -0.76, p < .001) but not saline (r(20) = -0.22, p = .36). Expectations for book listening-based analgesia did not significantly predict pain changes during saline (r(20) = -0.37, p = .11) or naloxone (r(18) = 0.26, p = .30) in the control group. CONCLUSIONS: These novel findings demonstrate a significant role for expectations in mindfulness-based pain relief. However, this role was minimal during saline and stronger during opioid blockade, despite similar pain reductions. This supports growing evidence that mindfulness engages multiple mechanisms to reduce pain, suggesting that mindfulness might be an effective pain-reducing technique even for individuals with low expectations for pain relief.

Interindividual differences in pain sensitivity vary as a function of interactions between sensory, cognitive-affective, and dispositional factors. Trait mindfulness, characterized as the innate capacity to nonreactively sustain attention to the present moment, is a psychological construct that is associated with lower clinical pain outcomes. Yet, the neural mechanisms supporting dispositional mindfulness are unknown. In an exploratory data analysis obtained during a study comparing mindfulness to placebo analgesia, we sought to determine whether dispositional mindfulness is associated with lower pain sensitivity. We also aimed to identify the brain mechanisms supporting the postulated inverse relationship between trait mindfulness and pain in response to noxious stimulation. We hypothesized that trait mindfulness would be associated with lower pain and greater deactivation of the default mode network. Seventy-six meditation-naive and healthy volunteers completed the Freiburg Mindfulness Inventory and were administered innocuous (35°C) and noxious stimulation (49°C) during perfusion-based functional magnetic resonance imaging. Higher Freiburg Mindfulness Inventory ratings were associated with lower pain intensity (P = 0.005) and pain unpleasantness ratings (P = 0.005). Whole brain analyses revealed that higher dispositional mindfulness was associated with greater deactivation of a brain region extending from the precuneus to posterior cingulate cortex during noxious heat. These novel findings demonstrate that mindful individuals feel less pain and evoke greater deactivation of brain regions supporting the engagement sensory, cognitive, and affective appraisals. We propose that mindfulness and the posterior cingulate cortex should be considered as important mechanistic targets for pain therapies.

Mindfulness meditation is a self-regulatory practice premised on sustaining nonreactive awareness of arising sensory events that reliably reduces pain. Yet, the specific analgesic mechanisms supporting mindfulness have not been comprehensively disentangled from the potential nonspecific factors supporting this technique. Increased parasympathetic nervous system (PNS) activity is associated with pain relief corresponding to a number of cognitive manipulations. However, the relationship between the PNS and mindfulness-based pain attenuation remains unknown. The primary objective of the present study was to determine the role of high-frequency heart rate variability (HF HRV), a marker of PNS activity, during mindfulness-based pain relief as compared to a validated, sham-mindfulness meditation technique that served as a breathing-based control. Sixty-two healthy volunteers (31 females; 31 males) were randomized to a 4-session (25 min/session) mindfulness or sham-mindfulness training regimen. Before and after each group's respective training, participants were administered noxious (49°C) and innocuous (35°C) heat to the right calf. HF HRV and respiration rate were recorded during thermal stimulation and pain intensity and unpleasantness ratings were collected after each stimulation series. The primary analysis revealed that during mindfulness meditation, higher HF HRV was more strongly associated with lower pain unpleasantness ratings when compared to sham-mindfulness meditation (B = -.82, P = .04). This finding is in line with the prediction that mindfulness-based meditation engages distinct mechanisms from sham-mindfulness meditation to reduce pain. However, the same prediction was not confirmed for pain intensity ratings (B = -.41). Secondary analyses determined that mindfulness and sham-mindfulness meditation similarly reduced pain ratings, decreased respiration rate, and increased HF HRV (between group ps < .05). More mechanistic work is needed to reliably determine the role of parasympathetic activation in mindfulness-based pain relief as compared to other meditative techniques. Perspective: Mindfulness has been shown to engage multiple mechanisms to reduce pain. The present study extends on this work to show that higher HRV is associated with mindfulness-induced reductions in pain unpleasantness, but not pain intensity ratings, when compared to sham-mindfulness meditation. These findings warrant further investigation into the mechanisms engaged by mindfulness as compared to placebo.

Pain and depressive mood commonly exhibit a comorbid relationship. Yet, the brain mechanisms that moderate the relationship between dysphoric mood and pain remain unknown. An exploratory analysis of functional magnetic resonance imaging, behavioral, and psychophysical data was collected from a previous study in 76 healthy, nondepressed, and pain-free individuals. Participants completed the Beck Depression Inventory-II (BDI), a measure of negative mood/depressive symptomology, and provided pain intensity and pain unpleasantness ratings in response to noxious heat (49°C) during perfusion-based, arterial spin-labeled functional magnetic resonance imaging. Moderation analyses were conducted to determine neural mechanisms involved in facilitating the hypothesized relationship between depressive mood and pain sensitivity. Higher BDI-II scores were positively associated with pain intensity (R = 0.10; P = 0.006) and pain unpleasantness (R = 0.12; P = 0.003) ratings. There was a high correlation between pain intensity and unpleasantness ratings (r = 0.94; P < 0.001); thus, brain moderation analyses were focused on pain intensity ratings. Individuals with higher levels of depressive mood exhibited heightened sensitivity to experimental pain. Greater activation in regions supporting the evaluation of pain (ventrolateral prefrontal cortex; anterior insula) and sensory-discrimination (secondary somatosensory cortex; posterior insula) moderated the relationship between higher BDI-II scores and pain intensity ratings. This study demonstrates that executive-level and sensory-discriminative brain mechanisms play a multimodal role in facilitating the bidirectional relationship between negative mood and pain.

The endogenous opioidergic system is critically involved in the cognitive modulation of pain. Slow-breathing-based techniques are widely used nonpharmacological approaches to reduce pain. Yet, the active mechanisms of actions supporting these practices are poorly characterized. Growing evidence suggest that mindfulness-meditation, a slow-breathing technique practiced by nonreactively attending to breathing sensations, engages multiple unique neural mechanisms that bypass opioidergically mediated descending pathways to reduce pain. However, it is unknown whether endogenous opioids contribute to pain reductions produced by slow breathing. The present double-blind, placebo-controlled crossover study examined behavioral pain responses during mindfulness-meditation (n = 19), sham-mindfulness meditation (n = 20), and slow-paced breathing (n = 20) in response to noxious heat (49°C) and intravenous administration (0.15 mg/kg bolus + 0.1 mg/kg/hour maintenance infusion) of the opioid antagonist, naloxone, and placebo saline. Mindfulness significantly reduced pain unpleasantness ratings across both infusion sessions when compared to rest, but not pain intensity. Slow-paced breathing significantly reduced pain intensity and unpleasantness ratings during naloxone but not saline infusion. Pain reductions produced by mindfulness-meditation and slow-paced breathing were insensitive to naloxone when compared to saline administration. By contrast, sham-mindfulness meditation produced pain unpleasantness reductions during saline infusion but this effect was reversed by opioidergic antagonism. Sham-mindfulness did not lower pain intensity ratings. Self-reported focusing on the breath was identified as the operational feature particularly unique to the mindfulness-meditation and slow paced-breathing, but not sham-mindfulness meditation. Across all individuals, attending to the breath was associated with naloxone insensitive pain-relief. These findings provide evidence that slow breathing combined with attention to breath reduces pain independent of endogenous opioids.