Neonatal Sleep Restriction Increases Nociceptive Sensitivity in Adolescent Mice

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dc.citation.issue2
dc.citation.volumev. 21
dc.contributor.authorAraujo, Paula [UNIFESP]
dc.contributor.authorCoelho, Cesar A. [UNIFESP]
dc.contributor.authorOliveira, Maria G. [UNIFESP]
dc.contributor.authorTufik, Sergio [UNIFESP]
dc.contributor.authorAndersen, Monica Levy [UNIFESP]
dc.coveragePaducah
dc.date.accessioned2020-07-20T16:31:19Z
dc.date.available2020-07-20T16:31:19Z
dc.date.issued2018
dc.description.abstractBackground: Sleep loss in infants may have a negative effect on the functional and structural development of the nociceptive system. We tested the hypothesis that neonatal sleep restriction induces a long-term increase of pain-related behaviors in mice and that this hypersensitivity occurs due to changes in the neuronal activity of nociceptive pathways. Objectives: We aim to investigate the effects of sleep loss in neonatal mice on pain behaviors of adolescent and adult mice in a sex-dependent manner. We also analyzed neuroanatomical and functional changes in pain pathways associated with behavioral changes. Study Design: An experimental animal study. Setting: A basic sleep research laboratory at Universidade Federal de Sao Paulo in Brazil. Methods: Neonatal mice at postnatal day (PND) 12 were randomly assigned to either control (CTRL), maternal separation (MS), or sleep restriction (SR) groups. MS and SR were performed 2 hours a day for 10 days (PND 12 until PND 21). The gentle handling method was used to prevent sleep. At PND 21, PND 35, or PND 90, the mice were tested for pain-related behaviors. Their brains were harvested and immunohistochemically stained for c-Fos protein in the anterior cingulate cortex, primary somatosensory cortex, and periaqueductal gray (PAG). Results: Neonatal SR significantly increased nociceptive sensitivity in the hot plate test in adolescent mice (-23.5% of pain threshold). This alteration in nociceptive response was accompanied by a decrease in c-Fos expression in PAG (-40% of c-Fos positive cells compared to the CTRL group). The hypersensitivity found in adolescent mice was not present in adult animals, and all mice showed a comparable nociceptive response. Limitations: Even using a mild manipulation method, in which a minimal amount of handling was applied to maintain wakefulness, sleep deprivation was a stressful event evidenced by higher corticosterone levels. Conclusion: Repeated exposures to sleep loss during early life were able to induce changes in the nociceptive response associated with alterations in neural activity in descending control of pain.en
dc.description.affiliationUniv Fed Sao Paulo UNIFESP, Dept Psicobiol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo UNIFESP, Dept Psicobiol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipAssociacao Fundo de Incentivo a Pesquisa (AFIP)
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP)
dc.description.sponsorshipNational Council for Scientific and Technological Development (CNPq)
dc.description.sponsorshipIDFAPESP: 10/50130-0
dc.description.sponsorshipIDFAPESP: 12/17619-0
dc.format.extentE137-E148
dc.identifierhttp://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=21&page=E137
dc.identifier.citationPain Physician. Paducah, v. 21, n. 2, p. E137-E148, 2018.
dc.identifier.issn1533-3159
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55875
dc.identifier.wosWOS:000429387100006
dc.language.isoeng
dc.publisherAm Soc Interventional Pain Physicians
dc.relation.ispartofPain Physician
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBrain maturationen
dc.subjecthypersensitivityen
dc.subjectneuronal activityen
dc.subjectnociceptionen
dc.subjectpainen
dc.subjectperiaqueductal grayen
dc.subjectpostnatal developmenten
dc.subjectsleepen
dc.subjectsleep deprivationen
dc.titleNeonatal Sleep Restriction Increases Nociceptive Sensitivity in Adolescent Miceen
dc.typeinfo:eu-repo/semantics/article
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