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Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial

Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sen...

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Autores principales: Irwin, Michael R., Olmstead, Richard, Bjurstrom, Martin F., Finan, Patrick H., Smith, Michael T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106531/
https://www.ncbi.nlm.nih.gov/pubmed/36314570
http://dx.doi.org/10.1097/j.pain.0000000000002811
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author Irwin, Michael R.
Olmstead, Richard
Bjurstrom, Martin F.
Finan, Patrick H.
Smith, Michael T.
author_facet Irwin, Michael R.
Olmstead, Richard
Bjurstrom, Martin F.
Finan, Patrick H.
Smith, Michael T.
author_sort Irwin, Michael R.
collection PubMed
description Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%]). The 2 sleep conditions were 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA, 8 pseudorandomly distributed awakenings and 200 minutes wake time during the 8-hour sleep opportunity), administered in a cross-over design after 2 weeks of washout and in a random order (FA-US; US-FA). Primary outcome was heat pain threshold (hPTH). Sleep architecture was assessed by polysomnography, and morning levels of cellular inflammation were evaluated by Toll-like receptor-4 stimulated monocyte intracellular proinflammatory cytokine production. As compared with US, FA was associated with decreases in the amount of slow wave or N3 sleep (P < 0.001), increases in Toll-like receptor-4 stimulated production of interleukin-6 and tumor necrosis factor-α (P = 0.03), and decreases in hPTH (P = 0.02). A comprehensive causal mediation analysis found that FA had an indirect effect on hPTH by decreases in N3 sleep and subsequent increases in inflammation (estimate=−0.15; 95% confidence interval, −0.30 to −0.03; P < 0.05) with the proportion mediated 34.9%. Differential loss of slow wave, N3 sleep, and increases in cellular inflammation are important drivers of pain sensitivity after sleep disruption. Clinical Trials Registration: NCT01794689.
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spelling pubmed-101065312023-04-18 Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial Irwin, Michael R. Olmstead, Richard Bjurstrom, Martin F. Finan, Patrick H. Smith, Michael T. Pain Research Paper Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%]). The 2 sleep conditions were 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA, 8 pseudorandomly distributed awakenings and 200 minutes wake time during the 8-hour sleep opportunity), administered in a cross-over design after 2 weeks of washout and in a random order (FA-US; US-FA). Primary outcome was heat pain threshold (hPTH). Sleep architecture was assessed by polysomnography, and morning levels of cellular inflammation were evaluated by Toll-like receptor-4 stimulated monocyte intracellular proinflammatory cytokine production. As compared with US, FA was associated with decreases in the amount of slow wave or N3 sleep (P < 0.001), increases in Toll-like receptor-4 stimulated production of interleukin-6 and tumor necrosis factor-α (P = 0.03), and decreases in hPTH (P = 0.02). A comprehensive causal mediation analysis found that FA had an indirect effect on hPTH by decreases in N3 sleep and subsequent increases in inflammation (estimate=−0.15; 95% confidence interval, −0.30 to −0.03; P < 0.05) with the proportion mediated 34.9%. Differential loss of slow wave, N3 sleep, and increases in cellular inflammation are important drivers of pain sensitivity after sleep disruption. Clinical Trials Registration: NCT01794689. Wolters Kluwer 2023-05 2022-10-27 /pmc/articles/PMC10106531/ /pubmed/36314570 http://dx.doi.org/10.1097/j.pain.0000000000002811 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Research Paper
Irwin, Michael R.
Olmstead, Richard
Bjurstrom, Martin F.
Finan, Patrick H.
Smith, Michael T.
Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial
title Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial
title_full Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial
title_fullStr Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial
title_full_unstemmed Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial
title_short Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial
title_sort sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106531/
https://www.ncbi.nlm.nih.gov/pubmed/36314570
http://dx.doi.org/10.1097/j.pain.0000000000002811
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