naloxone and Fatigue

We assessed the effects of naloxone, an opioid antagonist, on exercise capacity in 13 men and 5 women (mean age = 30.1 yr, range = 21-35 yr) during a 25 W/min incremental cycle ergometer test to exhaustion on different days during familiarization trial and then after 30 mg (iv bolus) of naloxone or placebo (Pl) in a double-blind, crossover design. Minute ventilation (Ve), O(2) consumption (Vo(2)), CO(2) production, and heart rate (HR) were monitored. Perceived exertion rating (0-10 scale) and venous samples for lactate were obtained each minute. Lactate and ventilatory thresholds were derived from lactate and gas-exchange data. Blood pressure was obtained before exercise, 5 min postinfusion, at maximum exercise, and 5 min postexercise. There were no control-Pl differences. The naloxone trial demonstrated decreased exercise time (96% Pl; P < 0.01), total cumulative work (96% Pl; P < 0.002), peak Vo(2) (94% Pl; P < 0.02), and HR (96% Pl; P < 0.01). Other variables were unchanged. HR and Ve were the same at the final common workload, but perceived exertion was higher (8.1 +/- 0.5 vs. 7.1 +/- 0.5) after naloxone than Pl (P < 0.01). The threshold for effort perception amplification occurred at approximately 60 +/- 4% of Pl peak Vo(2). Thus we conclude that peak work capacity was limited by perceived exertion, which can be attenuated by endogenous opioids rather than by physiological limits.

Topics: Adult; Blood Pressure; Cross-Over Studies; Exercise Test; Fatigue; Female; Heart Rate; Humans; Lactic Acid; Male; Naloxone; Narcotic Antagonists; Opioid Peptides; Oxygen Consumption; Perception; Physical Exertion; Sports

The effect on exercise performance and on the subjective perception of fatigue of the opioid receptor blocker naloxone, the nonselective beta-blocker timolol, and the combination of these two was studied in a double-blind randomized cycle ergometry test in healthy young men. Cumulative work at exhaustion was reduced by 25% after timolol (P less than 0.002) and by 34% after naloxone/timolol (P less than 0.02) but not after naloxone, compared with placebo. Naloxone alone had no influence on the subjective perception of fatigue (Borg scale rating), but significantly higher ratings were obtained by timolol and by naloxone/timolol. The present study does not support the hypothesis that opioid peptides are of importance for maximal exercise capacity and subjective perception of fatigue during short-term dynamic exercise in healthy young men.

Topics: Adult; Blood Glucose; Blood Pressure; Double-Blind Method; Exercise Test; Fatigue; Heart Rate; Humans; Male; Naloxone; Perception; Physical Exertion; Random Allocation; Timolol

Topics: Fatigue; Female; Humans; Liver Cirrhosis, Biliary; Middle Aged; Naloxone; Narcotic Antagonists; Substance Withdrawal Syndrome

In chronic experiments with rats during the exercises on a treadmill the ECG was registered and duration of the development of exhaustion was determined under control and under acute (1 mg/kg intraperitoneally 1 hour before the experiment) or chronic (1 mg/kg intraperitoneally, twice a day during 5 days) treatment with the opioid receptor antagonist naloxone. Chronic but not acute naloxone action resulted in increase of the fatiguability: the time of achievement of exhaustion decreased by 55.3% (P < 0.05). In this case the exhaustion developed at lower degree of heart rate than in control. Comparison of data obtained with the results of chronic treatment with the opioid antagonist permits to conclude that the chronic blockade increases the fatiguability to a great extent than chronic activation of opioid system. Possible mechanisms causing this difference are under discussion.

Topics: Acute Disease; Animals; Chronic Disease; Electrocardiography; Fatigue; Heart Rate; Male; Naloxone; Physical Exertion; Rats; Receptors, Opioid; Running

We studied monocyte function in 35 consecutive patients with chronic fatigue syndrome (CFS) and 25 healthy controls. Eighty-five per cent of the patients showed monocyte dysfunction characterized by marked reduction in the number of monocytes displaying immunoreactive cytoskeletal vimentin filaments, a low phagocytosis index, and a reduced expression of HLA-DR antigens. These values increased dramatically after incubation of the patients' monocytes with the opioid antagonist naloxone. Other immunological abnormalities also noted in the patients were low lymphocyte blastogenesis and diminished numbers of monocytes displaying receptors for Fc of IgG (FcR) and C3b (CR1). These findings suggest that an increased opioid activity acting through a classical receptor mechanism is active on monocytes from a high proportion of patients with CFS and that this represents a novel example of immunomodulation by opioid peptides in human disease. We suggest that endogenous opioids are involved in the pathogenesis of the chronic fatigue syndrome.

Topics: Adult; beta-Endorphin; Fatigue; Female; HLA-DR Antigens; Humans; Male; Middle Aged; Monocytes; Naloxone; Phagocytosis; Receptors, Complement; Receptors, Fc; Syndrome; Vimentin

Peromyscus maniculatus, deermice , were induced into daily torpor by restricting food to one-half daily ration. Intraperitoneal injection of naloxone (20 mg/kg) into mice habituated to daily IP injections of saline inhibited or modified the expression of daily torpor. In those individuals demonstrating long duration/deep bouts (greater than 300 min/body temperature 20 degrees C or below) naloxone administration resulted in 1) a significant decrease in the duration of torpor, 2) a significant elevation in minimum body temperatures attained during torpor and 3) a significant delay in the initiation time of torpor. In those individuals demonstrating short duration/shallow bouts (less than 300 min/body temperatures above 20 degrees C), naloxone administration resulted only in a significant delay of initiation time. Upon subsequent return to saline administration, however, these mice displayed a significant increase in the duration and depth of torpor. The results suggest that the endogenous opiates modulate the state of daily torpor.

Topics: Acclimatization; Animals; Fatigue; Naloxone; Peromyscus; Seasons; Stress, Physiological

Topics: Animals; Drug Interactions; Fatigue; Guinea Pigs; Ileum; In Vitro Techniques; Muscle Contraction; Naloxone

Topics: Adenine Nucleotides; Animals; Fatigue; Gastrointestinal Motility; Guinea Pigs; Ileum; In Vitro Techniques; Morphine; Naloxone; Peristalsis; Reflex