Mahler D A, Murray J A, Waterman L A, Ward J, Kraemer W J, Zhang X, Baird J C
Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School, Hanover, NH, USA.
Eur Respir J. 2009 Apr;33(4):771-7. doi: 10.1183/09031936.00145208. Epub 2009 Feb 12.
Exogenous opioid drugs, such as morphine, relieve breathlessness. The present study hypothesis was that endogenous opioids, released during the stress of exercise, modify dyspnoea in patients with chronic obstructive pulmonary disease. After familiarisation, patients performed an incremental treadmill exercise test followed by constant work on the treadmill for 10 min. At subsequent visits (2 to 3 days apart), patients received two puffs of albuterol, had a catheter placed in an arm vein for removal of blood to measure beta-endorphin immunoreactivity, received normal saline or 10 mg of naloxone intravenously in randomised order, and then performed high-intensity constant work rate exercise on the treadmill. The mean+/-sd age of the 17 patients (eight females and nine males) was 63+/-7 yrs, and post-bronchodilator forced expiratory volume in one second was 50+/-17% predicted. In both conditions, beta-endorphin levels increased three-fold from rest to end-exercise. The regression slope of breathlessness as a function of oxygen consumption (primary outcome), mean ratings of breathlessness throughout exercise and peak ratings of breathlessness were significantly higher with naloxone than normal saline. There were no differences in physiological responses throughout exercise between conditions. In conclusion, endogenous opioids modify dyspnoea during treadmill exercise in patients with chronic obstructive pulmonary disease by apparent alteration of central perception.
外源性阿片类药物，如吗啡，可缓解呼吸困难。本研究的假设是，在运动应激期间释放的内源性阿片类物质会改变慢性阻塞性肺疾病患者的呼吸困难症状。在熟悉流程后，患者进行递增式跑步机运动试验，随后在跑步机上持续工作10分钟。在随后的访视（间隔2至3天）中，患者吸入两喷沙丁胺醇，通过置于手臂静脉的导管取血以测量β-内啡肽免疫反应性，然后按随机顺序静脉注射生理盐水或10毫克纳洛酮，之后在跑步机上进行高强度恒定工作率运动。17例患者（8名女性和9名男性）的平均年龄为63±7岁，支气管扩张剂使用后一秒用力呼气量为预测值的50±17%。在两种情况下，β-内啡肽水平从静息状态到运动结束时均增加了三倍。与生理盐水相比，纳洛酮治疗时，作为耗氧量函数的呼吸困难回归斜率（主要结果）、运动期间呼吸困难的平均评分以及呼吸困难的峰值评分均显著更高。两种情况下运动期间的生理反应无差异。总之，内源性阿片类物质通过明显改变中枢感知来改变慢性阻塞性肺疾病患者跑步机运动期间的呼吸困难症状。
