Attention to breath sensations does not engage endogenous opioids to reduce 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.