Effects of Naloxone on Respiratory Sensation before and after a Removal of Severe Respiratory Stress

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Severe respiratory stress causes dyspnea and a sudden release of this stress frequently accompanies a euphoric sensation. We hypothesized that acute severe respiratory stress may result in elaboration of endogenous opioids within the central nervous system and that these opioids may play significant roles in relieving dyspnea and generating euphoric sensation after the sudden removal of severe respiratory stress. To test this hypothesis, we examined the effects of naloxone (0.04 mg/kg, i.v.) and placebo (normal saline) on changes in respiratory sensation before and after the release of severe respiratory stress in a double-blind, randomized, crossover study in 14 healthy adults. Acute severe respiratory stress was induced by loaded-breathing with a combination of resistive loading and hypercapnia. Subjects rated their changes in sensation using a bidirectional visual analogue scale. Naloxone pretreatment affected neither the ventilation nor the development of dyspneic sensation during loaded breathing. Naloloxone pretreatment attenuated only slightly the euphoric sensation developed after the release of severe respiratory stress. These findings suggest a small role of opioids in relieving dyspnea and generating euphoria before and after the sudden removal of severe respiratory stress.