title: Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD.
abstract: 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.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School, Hanover, NH, USA. Donald.a.mahler@hitchcock.org
authors.forename: D A
authors.initials: DA
authors.lastname: Mahler
authors.forename: J A
authors.initials: JA
authors.lastname: Murray
authors.forename: L A
authors.initials: LA
authors.lastname: Waterman
authors.forename: J
authors.initials: J
authors.lastname: Ward
authors.forename: W J
authors.initials: WJ
authors.lastname: Kraemer
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: J C
authors.initials: JC
authors.lastname: Baird
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000420:Albuterol / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage; D004311:Double-Blind Method; D004417:Dyspnea / Q000503:physiopathology*; D005080:Exercise Test; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D018847:Opioid Peptides / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D013147:Spirometry; D013806:Theophylline / Q000008:administration & dosage; D001615:beta-Endorphin / Q000097:blood
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D009270:Naloxone; D001615:beta-Endorphin; D013806:Theophylline; D000420:Albuterol