Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD

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

^* To whom correspondence should be addressed. E-mail: Donald.a.mahler{at}hitchcock.org.

	Abstract

Exogenous opioid drugs, such as morphine, relieve breathlessness. Our hypothesis is that endogenous opioids, released during the stress of exercise, modify dyspnoea in patients with chronic obstructive pulmonary disease.

After familiarization, patients performed an incremental treadmill exercise test followed by constant work on the treadmill for 10 minutes. At subsequent visits (2 to 3 days apart): patients received 2 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 randomized order; and then performed high intensity constant work rate exercise on treadmill.

Age of the seventeen patients (8 females/9 males) was 63±7 years, and post-bronchodilator FEV₁ 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.

We conclude that endogenous opioids modify dyspnoea during treadmill exercise in patients with chronic obstructive pulmonary disease by apparent alteration of central perception.