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Original Research: Signs and Symptoms of Chest Diseases |

Effect of Increased Blood Levels of β-Endorphin on Perception of BreathlessnessEffect of 03B2-Endorphin on Breathlessness

Donald A. Mahler, MD, FCCP; Alex H. Gifford, MD; Laurie A. Waterman, MS; Joseph Ward, RCPT; William J. Kraemer, PhD; Brian R. Kupchak, PhD; Andrew Harver, PhD
Author and Funding Information

From the Section of Pulmonary and Critical Care Medicine (Drs Mahler and Gifford) and the Pulmonary Function and Cardiopulmonary Exercise Laboratories (Ms Waterman and Mr Ward), Dartmouth-Hitchcock Medical Center, Lebanon, NH; the Department of Kinesiology and the Department of Physiology and Neurobiology (Drs Kraemer and Kupchak), University of Connecticut, Storrs, CT; and the Department of Public Health Sciences (Dr Harver), University of North Carolina at Charlotte, Charlotte, NC.

Correspondence to: Donald A. Mahler, MD, FCCP, Section of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756; e-mail: Donald.a.mahler@hitchcock.org


Funding/Support: This study was supported by the Hitchcock Foundation (Dr Mahler).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(5):1378-1385. doi:10.1378/chest.12-1541
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Background:  Although opioid receptors are expressed broadly in the CNS and in peripheral sensory nerve endings including bronchioles and alveolar walls of the respiratory tract, it is unknown whether the modulatory effect of endogenous opioids on breathlessness occurs in the CNS or in the peripheral nervous system. The purpose of this investigation was to examine whether increased blood levels of β-endorphin modify breathlessness by a putative effect of binding to peripheral opioid receptors in the respiratory tract.

Methods:  Twenty patients with COPD (10 women and 10 men; age, 70 ± 8 years) inspired through resistances during practice sessions to identify an individualized target load that caused ratings of intensity and unpleasantness of breathlessness ≥ 50 mm on a 100-mm visual analog scale. At two interventions, blood levels of β-endorphin and adrenocorticotropic hormone (ACTH) were measured, ketoconazole (600 mg) or placebo was administered orally, and patients rated the two dimensions of breathlessness each minute during resistive load breathing (RLB).

Results:  By inhibiting cortisol synthesis, ketoconazole led to significant increases in β-endorphin (mean change, 20% ± 4%) and ACTH (mean change, 21% ± 4%) compared with placebo. The intensity and unpleasantness ratings of breathlessness and the endurance time during RLB were similar in the two interventions.

Conclusions:  The previously demonstrated modulatory effect of endogenous opioids on breathlessness appears to be mediated by binding to receptors within the CNS rather than to peripheral opioid receptors in the respiratory tract. An alternative explanation is that the magnitude of the β-endorphin response is inadequate to affect peripheral opioid receptors.

Trial Registry:  ClinicalTrials.gov; No.: NCT01378520; URL: www.clinicaltrials.gov

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