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Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD

¹ Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School, , Hanover, NH, ³ Pulmonary Function and Cardiopulmonary Exercise Laboratories, Dartmouth-Hitchcock Medical Center, , Lebanon, NH, ² Unity Health System, , Rochester, NY, ⁴ University of Connecticut, , Storrs, CT, and ⁵ Psychological Applications, , South Pomfret, VT, USA.

CORRESPONDENCE: D. A. Mahler, , Section of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, , One Medical Center Drive, Lebanon, NH 03756-0001, USA. Fax: 1 6036500580. E-mail: Donald.a.mahler{at}hitchcock.org

Keywords: β-endorphin immunoreactivity, chronic obstructive pulmonary disease, continuous ratings of breathlessness, naloxone, treadmill exercise

Received: September 23, 2008
Accepted December 1, 2008

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 β-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, β-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.