beta-endorphin and Sleep-Apnea-Syndromes

Previous studies have indicated increased immunoreactivity of the endogenous opioid peptide beta-endorphin in the cerebrospinal fluid (CSF) of infants under 2 years of age with apnea. To assess the role of endogenous opioids in the pathogenesis of apnea in children, the effect of oral treatment with the opioid antagonist naltrexone was studied in apneic infants, as well as in older apneic children, with demonstrated increases in CSF immunoreactive beta-endorphin (i-BE). In the 8 apneic infants with elevated i-BE in lumbar CSF (range, 55-155 pg/ml; normal, 17-52 pg/ml), no further apnea occurred during naltrexone therapy (1 mg/kg/day, by mouth). Five children (2-8 years old) with apnea of unknown cause had elevated CSF i-BE (range, 74-276 pg/ml) compared to 6 age-matched nonapneic children (range, 15-48 pg/ml). No apneic events occurred during naltrexone therapy, except in 1 child during stressful events, but apnea recurred in some patients after attempts to discontinue naltrexone treatment. Adverse effects of naltrexone included complaints of headaches in 2 children and symptoms of a narcotic withdrawal syndrome during the first 3 days of treatment in 1 child. Three children with Leigh's syndrome had elevated CSF i-BE (range, 104-291 pg/ml) and their apnea also responded to naltrexone. We conclude that elevated endogenous opioids contribute to the pathogenesis of apnea in children and may even result in physical dependence.

Topics: beta-Endorphin; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Leigh Disease; Male; Naltrexone; Prospective Studies; Sleep Apnea Syndromes

The etiology of the SAS is unknown. To test whether endogenous opioids could be pathologically active in SAS, markers of opioid systems were measured in the CSF of 15 patients with SAS and in control subjects. Measured by receptor assay, the concentration of so-called fraction 1 opioid was higher in patients with SAS (3.0 +/- 1.5 pmol/ml; mean +/- SD) than in control subjects (1.1 +/- 0.5 pmol/ml) (p less than 0.01), whereas that of fraction 2 opioid was similar in the two groups. Beta-endorphin-like activity, measured by radioimmunoassay, was somewhat lower in patients with SAS (14.0 +/- 2.8 pmol/ml) than in control subjects (21.8 +/- 7.6 pmol/ml) (p less than 0.05). Six months after surgical treatment of the soft palate, new measurements were made in eight patients. Fraction 2 endorphin and beta-endorphin showed no consistent changes. A decrease in the level of fraction 1 from 4.1 +/- 1.5 pmol/ml to 2.3 +/- 1.0 pmol/ml (p less than 0.02) was noted in those six patients showing a successful clinical course. The data support the hypothesis that in SAS the opioid activity is increased.

Topics: Adult; beta-Endorphin; Endorphins; Female; Humans; Male; Middle Aged; Palate, Soft; Postoperative Period; Sleep Apnea Syndromes; Spirometry

To test the hypothesis that endogenous opiates play a role in the etiology of the sleep apnea syndrome, we administered naloxone, an opiate antagonist, to ten obese humans with sleep apnea. On two separate nights we measured the frequency and severity of sleep apnea during naloxone infusion vs saline control infusion. The number of oxyhemoglobin desaturation episodes was not significantly lowered but the average maximal oxyhemoglobin desaturation fell significantly (P less than 0.01) with naloxone. The desaturation index (average maximal oxyhemoglobin desaturation times desaturations per hour) fell by 21 percent (P less than 0.05) on the night of naloxone infusion. Nine of the ten patients had a lower desaturation index with naloxone. REM sleep decreased by 80 percent (P less than 0.05) in the subjects in whom it was measured. We conclude that opiate antagonists hold promise in the treatment of sleep apnea and that the endogenous opiate system may be involved in the production of sleep apnea.

Topics: beta-Endorphin; Endorphins; Female; Humans; Male; Naloxone; Obesity; Sleep Apnea Syndromes; Sleep, REM

Topics: beta-Endorphin; Endorphins; Female; Humans; Infant; Male; Sleep Apnea Syndromes; Sudden Infant Death