Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by recurrent nocturnal hypoxia and sleep disruption. Sleep fragmentation caused hyperalgesia in volunteers, while nocturnal hypoxemia enhanced morphine analgesic potency in children with OSA. This evidence directly relates to surgical OSA patients who are at risk for airway compromise due to postoperative use of opioids. Using accepted experimental pain models, we characterized pain processing and opioid analgesia in male volunteers recruited based on their risk for OSA. METHODS: After approval from the Intitutional Review Board and informed consent, we assessed heat and cold pain thresholds and tolerances in volunteers after overnight polysomnography (PSG). Three pro-inflammatory and 3 hypoxia markers were determined in the serum. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 µg/ml), an µ-opioid agonist. Linear mixed effects regression models were employed to evaluate the association of 3 PSG descriptors [wake after sleep onset, number of sleep stage shifts, and lowest oxyhemoglobin saturation (SaO(2)) during sleep] and all serum markers with pain thresholds and tolerances at baseline, as well as their changes under remifentanil. RESULTS: Forty-three volunteers (12 normal and 31 with a PSG-based diagnosis of OSA) were included in the analysis. The lower nadir SaO(2) and higher insulin growth factor binding protein-1 (IGFBP-1) were associated with higher analgesic sensitivity to remifentanil (SaO(2), P = 0.0440; IGFBP-1, P = 0.0013). Other pro-inflammatory mediators like interleukin-1ß and tumor necrosis factor-α (TNF-α) were associated with an enhanced sensitivity to the opioid analgesic effect (IL-1ß, P = 0.0218; TNF-α, P = 0.0276). CONCLUSIONS: Nocturnal hypoxemia in subjects at high risk for OSA was associated with an increased potency of opioid analgesia. A serum hypoxia marker (IGFBP-1) was associated with hypoalgesia and increased potency to opioid analgesia; other pro-inflammatory mediators also predicted an enhanced opioid potency. TRIAL REGISTRATION: Clinicaltrials.gov NCT00672737.

Epidemiology of sleep-related complaints associated with sleep-disordered breathing in Bangkok, Thailand.

BACKGROUND: This study assesses the prevalence of and risk factors for sleep-related complaints in Bangkok, Thailand. METHODS: A representative sample of the Bangkok population was selected based on results of the 2000 Census. A total of 4680 participants underwent face-to-face interview with a 49-question sleep inventory. RESULTS: Four percent of the total sampled (5.3% of men and 3.5% of women) complained of habitual snoring (>3 nights/week) and excessive daytime sleepiness (>3 days/week) for at least 3 months. These subjects were significantly (p<0.0001) older (41.4 vs. 36.7 years), had greater BMI (26.0 vs. 22.8 kg/m(2)), neck size (34.7 vs. 32.5 cms), and waist circumference (88.0 vs. 78.7 cms). They reported significantly shorter nocturnal sleep time, greater frequency of sleep disturbances and awakenings, unrefreshing sleep, choking during sleep, night sweats, nocturia, and bruxism. There was also a greater prevalence of cardiovascular and endocrine diseases. Multivariate analysis showed that male gender; BMI; waist size; and reports of witnessed apneas, unrefreshing sleep and night sweats were significant predictors of snoring and daytime sleepiness. CONCLUSION: This is the first epidemiologic study investigating sleep-related complaints and associated health morbidities in the Thai population.

c-Fos immunoreactivity in the brain after esophageal acid stimulation.

The goal of this study was to use c-Fos immunohistochemistry to establish a rat model for studying the central projection of the esophageal afferent neurons during acid exposure. A cannula was placed in the esophagus of anesthetized Wistar rats with the tip approximately 2 cm above the lower esophageal sphincter (LES). Hydrochloric acid (0.1 N HCl, 50 mmol/L) with pepsin (3,200-4,500 U/mL), at pH 1.6, was then perfused into the esophagi of the experimental rats (n = 8) at 10 mL/hr continuously for 50 minutes. Normal saline solution (0.9% NaCl) was used in control rats (n = 6), and home cage control animals (n = 6) were given no stimulation. Thirty minutes after the perfusion, the rat was killed and the brain was removed and processed for c-Fos immunohistochemistry. A transverse section of the esophagus, 2 cm above the LES, was stained with hematoxylin and eosin stain for light microscopy. c-Fos immunoreactivity was significantly increased in a number of brain regions in the rats receiving the acid plus pepsin perfusion. These areas included the central amygdala, the Kölliker-Fuse nucleus, the nucleus of the solitary tract (NTS), the medial part of the NTS, the interstitial part of the NTS, the commissural part of the NTS, the paratrigeminal nucleus, the ambiguus nucleus, and the rostroventrolateral recticular nucleus. Perfusion with acid-pepsin solution also resulted in morphologic changes in the esophagus on light microscopy. This study suggests that acid plus pepsin perfusion of esophagus results in both neural activation in areas of the central nervous system and damage to the esophagus in an animal model.