Effect of Increased Blood Levels of β-Endorphin on Perception of Breathlessness
| Autor: | Donald A. Mahler, William J. Kraemer, Brian R. Kupchak, Laurie A. Waterman, Joseph Ward, Alex H. Gifford, Andrew Harver |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_specialty medicine.drug_class Respiratory System Adrenocorticotropic hormone Substance P Critical Care and Intensive Care Medicine Placebo Severity of Illness Index Pulmonary Disease Chronic Obstructive chemistry.chemical_compound Adrenocorticotropic Hormone Opioid receptor Internal medicine medicine Humans Aged Endogenous opioid business.industry beta-Endorphin Middle Aged Dyspnea Ketoconazole Treatment Outcome medicine.anatomical_structure Endocrinology chemistry Opioid Peripheral nervous system Anesthesia Receptors Opioid Female Cardiology and Cardiovascular Medicine business Biomarkers Respiratory tract medicine.drug |
| Zdroj: | Chest. 143:1378-1385 |
| ISSN: | 0012-3692 |
| DOI: | 10.1378/chest.12-1541 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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