naloxone and Pulmonary-Disease--Chronic-Obstructive

To review the mechanisms for the perception of dyspnea and to consider the plausibility of interventions that palliate dyspnea after optimal treatment of the underlying disease.. Activation of sensory receptors by blood gas abnormalities, mechanical respiratory loads, and hyperinflation provides afferent information to the central nervous system for integration and processing. It has been proposed that a discriminative pathway processes afferent impulses to the somatosensory cortex that reflects the intensity of dyspnea, whereas an affective pathway projects afferent impulses to structures of the limbic system that reflects the unpleasantness of dyspnea. In one study, patients with chronic obstructive pulmonary disease reported consistently higher ratings of breathlessness after administration of naloxone, an opioid receptor antagonist, compared with physiological saline during high-intensity treadmill exercise. This finding supports the role of endogenous opioids in modulating dyspnea. Nebulized furosemide, anti-inflammatory therapy, and chest wall vibration are potential approaches for modulating lung and chest wall receptors to relieve dyspnea.. Targets for palliating dyspnea in patients with advanced disease include sensory receptors within the lung/chest wall and the central nervous system. The opioid system plays an important role in palliating dyspnea. Both endogenous (β-endorphins) and exogenous (morphine) opioids modulate breathlessness.

Topics: Afferent Pathways; Central Nervous System; Dyspnea; Efferent Pathways; Endorphins; Humans; Naloxone; Narcotic Antagonists; Neurotransmitter Agents; Palliative Care; Panic Disorder; Pulmonary Disease, Chronic Obstructive; Sensory Receptor Cells

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

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

Topics: Humans; Naloxone; Noninvasive Ventilation; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Ventilators, Mechanical

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

Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Dyspnea; Female; Humans; Male; Naloxone; Narcotic Antagonists; Palliative Care; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency