[Role of endogenous opioids in respiratory control system and dyspnea sensation in healthy adult humans].

To clarify whether endogenous opioids play modulatory roles in control of breathing and have any specific effects on the intensity of dyspnea, healthy volunteers were examined for two protocols of ventilatory response tests. 1) The ventilatory response to hypercapnic progressive hypoxia and the withdrawal response to assess peripheral chemoreceptor activity were compared before and after intravenous infusion of 3 mg naloxone in 21 healthy adults. The average ventilatory response increased significantly after naloxone infusion (p less than 0.05), whereas there were no significant changes between two tests with normal saline in the control study (n = 7). Because there was considerable interindividual variation in the response to naloxone administration, "high responders" (n = 8) who showed larger increases with naloxone than the upper limit of the 95% confidence interval for the change with the second saline in the control study were selected. They showed greater ventilatory responses before naloxone infusion than did the other subjects (p less than 0.01). There was no significant change in the withdrawal response before and after naloxone infusion, even in such high responders. 2) The ventilatory and peak mouth pressure responses to hypoxic progressive hypercapnia with inspiratory flow-resistive loading were measured after the intravenous infusion of 3 mg naloxone or saline in 11 male volunteers, while the intensity of dyspnea was simultaneously assessed. Naloxone administration increased the peak mouth pressure response (p less than 0.05) although the increase in ventilatory response did not reach statistical significance. The intensity of dyspnea tended to be greater after naloxone infusion than after saline infusion at end-tidal PCO2 levels of 55 Torr and 60 Torr (p = 0.06 and 0.09, respectively). However, the intensity of dyspnea was quite similar between trials with and without naloxone when compared at equivalent levels of either minute ventilation or peak mouth pressure. These findings suggest that endogenous opioids suppress respiratory outputs under a strong, acute respiratory stress in normal humans. This may be particularly true for those subjects who have greater chemosensitivity. Endogenous opioids appear to act centrally rather than peripherally, but do not have any specific modulatory role on the sensation of dyspnea.