LAUSR

The endogenous opioidergic system is critically involved in the cognitive modulation of pain. Slow-breathing based techniques are widely utilized non-pharmacological approaches to reduce pain, although the active mechanisms of actions supporting these practices are poorly characterized. Growing evidence suggest that mindfulness-meditation, a slow-breathing technique practiced by non-reactively attending to breathing sensations, engages multiple unique neural mechanisms that bypass opioidergically mediated descending pathways to reduce pain. Yet, it is unknown if 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/h 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 lower pain intensity and unpleasantness ratings during naloxone but not saline. Pain reductions produced by mindfulness-meditation and slow-paced breathing were insensitive to naloxone when compared to saline infusion. In 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.