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

<h4>Background</h4>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...

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Autores principales:	Anthony G Doufas, Lu Tian, Kevin A Padrez, Puntarica Suwanprathes, James A Cardell, Holden T Maecker, Periklis Panousis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7881774612c04ee18f8a0b7a580e41a2
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spelling	oai:doaj.org-article:7881774612c04ee18f8a0b7a580e41a22021-11-18T07:59:41ZExperimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.1932-620310.1371/journal.pone.0054807https://doaj.org/article/7881774612c04ee18f8a0b7a580e41a22013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23382975/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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-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).<h4>Conclusions</h4>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.<h4>Trial registration</h4>Clinicaltrials.gov NCT00672737.Anthony G DoufasLu TianKevin A PadrezPuntarica SuwanprathesJames A CardellHolden T MaeckerPeriklis PanousisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54807 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anthony G Doufas Lu Tian Kevin A Padrez Puntarica Suwanprathes James A Cardell Holden T Maecker Periklis Panousis Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.
description	<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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-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).<h4>Conclusions</h4>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.<h4>Trial registration</h4>Clinicaltrials.gov NCT00672737.
format	article
author	Anthony G Doufas Lu Tian Kevin A Padrez Puntarica Suwanprathes James A Cardell Holden T Maecker Periklis Panousis
author_facet	Anthony G Doufas Lu Tian Kevin A Padrez Puntarica Suwanprathes James A Cardell Holden T Maecker Periklis Panousis
author_sort	Anthony G Doufas
title	Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.
title_short	Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.
title_full	Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.
title_fullStr	Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.
title_full_unstemmed	Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.
title_sort	experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7881774612c04ee18f8a0b7a580e41a2
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Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.

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