Endorphins and the Control of Breathing: Ability of Naloxone to Restore Flow-Resistive Load Compensation in Chronic Obstructive Pulmonary Disease

Since narcotic drugs profoundly depress breathing, we tested whether endogenous opioids influenced control of breathing in chronic obstructive pulmonary disease (COPD), reasoning that the stress of chronic dyspnea might cause elaboration of “endorphins.” In 14 patients with COPD (but without respiratory failure) and eight normal controls, we measured ventilation, mechanical lung function, respiratory sensitivity to carbon dioxide, and the increase in respiratory effort elicited by an increase in resistance to breathing; each measurement was performed before and after administration of the opiate antagonist naloxone. Before naloxone, increased resistance to breathing enhanced respiratory effort in all controls, but seven of 14 patients with COPD had no response. After naloxone, these seven patients had load responses. Furthermore, the respiratory effort elicited by the resistance also increased after the drug was given to the patients who had had a response. These data suggest that endorphin elaboration minimizes the stress of chronic airway obstruction. (N Engl J Med. 1981; 304:1190–5.). IT is generally agreed that opiate-agonists that are endogenously produced by the central nervous system have an important role in several pathophysiologic systems. These “endorphins” * have been postulated to be involved in such diverse circumstances as the responses to chronic pain¹ and neuroendocrine regulation.² However, despite the wellknown, potent effects of exogenous opiates on respiration^3,4 and the documentation of plentiful opiate receptors in the medulla,⁵ no role for endorphins in human respiratory control has been found. Indeed, it appears that they are not involved in the chemical control of breathing in normal subjects.⁶ In this study, we tested whether elaboration. . .