beta-endorphin and Pulmonary-Disease--Chronic-Obstructive

Neuromuscular electrical stimulation (NMES) improves muscle performance and exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. In contrast, no study has assessed the effect of NMES on dynamic hyperinflation (DH) in COPD. This study investigated the effect of short-term, high-frequency NMES on DH in patients with COPD.. Twenty patients were randomly allocated to either a NMES applied bilaterally to the quadriceps muscles (n = 11: 8 weeks, 5 days/week, twice/day, 45 min/session) or a control group (n = 09). All patients received respiratory physical therapy and stretching exercises. Free fat mass, pulmonary function, time to exercise tolerance (Tlim), 6-min walk test distance (6-MWTD), tumor necrosis factor (TNF-α) and β-endorphin levels, Borg dyspnea and leg score (BDS and BLS) and quality of life by the St. George's Respiratory Questionnaire score (SGRQ) were examined before and after the intervention.. Compared with the control group, NMES increased FEV1 and FEV1/FVC, 6-MWD and Tlim (P < 0.01) and reduced BDS and SGRQ (P < 0.01). Additionally, changes in the Tlim were positively correlated with respiratory improvements in FEV1 (rho = 0.48, P < 0.01). Also, NMES reduced TNF-α and increased β-endorphin levels, compared with the control group (P < 0.001).. In summary, 8 weeks of NMES promotes reduction of the perceived sensation of dyspnea during exercise in patients with COPD. This finding is accompanied by improvements in FEV1, exercise tolerance and quality of life, and DH. Interestingly, these findings may be associated with enhanced vasodilatory function and a reduction in inflammatory responses.. NCT01695421.

Topics: Adult; Aged; Anthropometry; beta-Endorphin; Body Composition; Double-Blind Method; Electric Stimulation Therapy; Exercise Test; Exercise Tolerance; Humans; Inspiratory Capacity; Male; Middle Aged; Muscle Strength; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Quadriceps Muscle; Quality of Life; Respiratory Mechanics; Respiratory Muscles; Tumor Necrosis Factor-alpha

The objective of this study was to investigate whether substance P, an excitatory neuropeptide, modulates the perception of breathlessness by administering aprepitant, a selective antagonist that blocks neurokinin (NK)-1 receptor signaling. Individual targeted resistive load breathing (RLB) was used to provoke breathlessness. In Study 1, sixteen patients (age, 70±6 years) with chronic obstructive pulmonary disease (COPD) reported similar ratings of breathlessness during RLB between oral aprepitant (125mg) and placebo. After aprepitant, but not with placebo, there were significant increases in blood levels of substance P (+54±39%) and beta-endorphin (+27±17%). A similar design was used in Study 2 except that naloxone (10mg) was administered intravenously prior to RLB to block any effect of endogenous opioids. Nine patients with COPD reported comparable breathlessness ratings during RLB between aprepitant and placebo. Our results do not support a role for the substance P-NK-1 pathway in the perception of breathlessness in patients with COPD. With selective antagonism of NK-1 signaling, there was co-transmission of substance P and beta-endorphin neuropeptides.

Topics: Aged; Aprepitant; beta-Endorphin; Double-Blind Method; Dyspnea; Female; Humans; Male; Morpholines; Naloxone; Narcotic Antagonists; Neurokinin-1 Receptor Antagonists; Perception; Pulmonary Disease, Chronic Obstructive; Respiration; Substance P; Time Factors; Treatment Outcome

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.. 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).. 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.. 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.. ClinicalTrials.gov; No.: NCT01378520; URL: www.clinicaltrials.gov.

Topics: Adrenocorticotropic Hormone; Aged; beta-Endorphin; Biomarkers; Dyspnea; Female; Humans; Ketoconazole; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Receptors, Opioid; Respiratory System; Severity of Illness Index; Substance P; Treatment Outcome

Our recent studies showed that one session of transcutaneous electrical nerve stimulation on acupoints (Acu-TENS) improved forced expiratory volume in 1s (FEV(1)) in patients with chronic obstructive pulmonary disease (COPD). This study investigated the effect of 4-week Acu-TENS on physical and psychosocial function in these patients. Twenty-eight patients were randomly allocated to receive 4-weeks of 45-min, 5-days/week, of either Acu-TENS (over Dingchuan), Placebo-TENS (same protocol without electrical output), or Sham-TENS (over the patellae). Variables measured before and after intervention included FEV(1), forced vital capacity (FVC), 6-min walk distance (6MWD), St. George's Respiratory Questionnaire score (SGRQ), beta-endorphin and blood inflammatory marker levels. Only the Acu-TENS group attained significant improvement in FEV(1) (p=0.046), physical activity (p=0.007) and total SGRQ score (p=0.028). The increase in beta-endorphin (p=0.012) correlated positively with the improvement in FEV(1) (r=0.526, p=0.008). To conclude, 4 weeks of Acu-TENS improved the functional capacity of patients with COPD, probably due to the bronchodilation induced by beta-endorphin elevation.

Topics: Acupuncture Points; Aged; Analysis of Variance; beta-Endorphin; C-Reactive Protein; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Interleukin-8; Male; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Surveys and Questionnaires; Time Factors; Transcutaneous Electric Nerve Stimulation; Treatment Outcome; Tumor Necrosis Factor-alpha; Vital Capacity

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.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; beta-Endorphin; Bronchodilator Agents; Double-Blind Method; Dyspnea; Exercise Test; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid Peptides; Oxygen Consumption; Pulmonary Disease, Chronic Obstructive; Spirometry; Theophylline

Application of transcutaneous electrical nerve stimulation over acupuncture points (Acu-TENS) is a noninvasive intervention that has recently been shown to alleviate dyspnea in patients with stable chronic obstructive pulmonary disease (COPD). This case report aims to explore the role of Acu-TENS in patients diagnosed with COPD during the acute exacerbation.. The study design was a case report.. The study was conducted in an inpatient setting.. The subject was a 74-year-old man admitted to the hospital due to acute exacerbation of COPD (AECOPD).. Treatment consisted of application of TENS on EX-B1 (Dingchuan) for 45 minutes.. Oxygen saturation, heart rate, and dyspnea score were measured before, immediately after, and 45 minutes after Acu-TENS intervention. Other than the physiologic measures, 10 mL of venous blood was taken from the cubital vein for assessment of β-endorphin level, white blood cell count, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) level before and immediately postintervention.. Postintervention, improved oxygen saturation, and reduction in heart rate and dyspneic sensation were observed accompanied by a raised blood β-endorphin level but the level of white blood cell count, TNF-α, and CRP remain unchanged.. Application of 45 minutes Acu-TENS appeared to alleviate symptoms in a patient with AECOPD. The role of adjunctive Acu-TENS therapy during acute exacerbation warrants further investigation.

Topics: Acupuncture Points; Acute Disease; Aged; beta-Endorphin; C-Reactive Protein; Dyspnea; Heart Rate; Humans; Leukocyte Count; Male; Outcome Assessment, Health Care; Oxygen; Pulmonary Disease, Chronic Obstructive; Transcutaneous Electric Nerve Stimulation; Tumor Necrosis Factor-alpha

Endogenous opioids are naturally occurring peptides released by the brain in response to noxious stimuli. Although these naturally occurring peptides modulate pain, it is unknown whether endogenous opioids affect the perception of breathlessness associated with a specific respiratory challenge. The hypothesis is that intravenous administration of naloxone, used to block opioid signaling and inhibit neural pathways, will increase ratings of breathlessness during resistive load breathing (RLB) in patients with chronic obstructive pulmonary disease (COPD).. Fourteen patients with COPD (age, 64 ± 9 years) inspired through resistances during practice sessions to identify an individualized target load that caused ratings of intensity and/or unpleasantness of breathlessness ≥ 50 mm on a 100 mm visual analog scale. At two intervention visits, serum beta-endorphins were measured, naloxone (10 mg/25 ml) or normal saline (25 ml) was administered intravenously, and patients rated the two dimensions of breathlessness each minute during RLB.. Patient ratings of intensity (p = 0.0004) and unpleasantness (p = 0.024) of breathlessness were higher with naloxone compared with normal saline. Eleven patients (79%) reported that it was easier to breathe during RLB with normal saline (p = 0.025). RLB led to significant increases in serum beta-endorphin immunoreactivity and decreases in inspiratory capacity. There were no significant differences in physiological responses between interventions.. Endogenous opioids modulate the intensity and the unpleasantness of breathlessness in patients with COPD. Differences in breathlessness ratings between interventions were clinically relevant based on the patients' global assessment.

Topics: Aged; Airway Resistance; beta-Endorphin; Cross-Over Studies; Double-Blind Method; Dyspnea; Female; Humans; Inspiratory Capacity; Male; Middle Aged; Naloxone; Narcotic Antagonists; Pulmonary Disease, Chronic Obstructive; Random Allocation; Respiration