Abstract
BackgroundObstructive 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.MethodsAfter 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 (SaO2) during sleep] and all serum markers with pain thresholds and tolerances at baseline, as well as their changes under remifentanil.ResultsForty-three volunteers (12 normal and 31 with a PSG-based diagnosis of OSA) were included in the analysis. The lower nadir SaO2 and higher insulin growth factor binding protein-1 (IGFBP-1) were associated with higher analgesic sensitivity to remifentanil (SaO2, P = 0.0440; IGFBP-1, P = 0.0013). Other pro-inflammatory mediators like interleukin-1β and tumor necrosis factor-α (TNF-α) were associated with an enhanced sensitivity to the opioid analgesic effect (IL-1β, P = 0.0218; TNF-α, P = 0.0276).ConclusionsNocturnal 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.
Highlights
Obstructive sleep apnea (OSA) is a common health condition [1,2] characterized by cyclic cessations of airflow due to intermittent complete or partial airway obstruction, leading to episodic hypoxia and repeated arousals from sleep [3]
Children suffering from obstructive sleep apnea (OSA) demonstrated an increased sensitivity to the postoperative analgesic effect of morphine; interestingly, morphine dose requirement for postoperative pain was inversely proportional to the degree of nocturnal hypoxemia preoperatively [34,35]
We examined the effect of sleep disruption and nocturnal hypoxemia on pain behavior and opioid analgesia
Summary
Obstructive sleep apnea (OSA) is a common health condition [1,2] characterized by cyclic cessations of airflow due to intermittent complete or partial airway obstruction, leading to episodic hypoxia and repeated arousals from sleep [3]. Important phenotypic components of sleep-disordered breathing, like sleep disruption, recurrent nocturnal hypoxemia, and systemic inflammation [18], have been linked to altered pain processing Both experimental [19,20,21] and clinical [22,23] evidence suggest that inadequate and/or disrupted sleep could enhance pain sensitivity in humans, while prolonged deprivation of sleep promoted the expression [24] and release of major sleepregulating cytokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6 [25,26,27,28,29,30], which are known to exert hyperalgesic effects in various experimental models [31,32]. Using accepted experimental pain models, we characterized pain processing and opioid analgesia in male volunteers recruited based on their risk for OSA
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