Evidence map›Paper›PMID 33341652›Full record

ArticleNeurobiology of aging2021

Postoperative cognitive dysfunction is made persistent with morphine treatment in aged rats.

Stephanie M Muscat, Nicholas P Deems, Heather D'Angelo, Meagan M Kitt, Peter M Grace, Nathan D Andersen, Shaelyn N Silverman, Kenner C Rice, Linda R Watkins, Steven F Maier and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 55 citations in OpenAlex.

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  16. CD8Brain, behavior, and immunity · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

Stephanie M MuscatInstitute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA; Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, USA.
Nicholas P DeemsInstitute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA; Neuroscience Graduate Program, The Ohio State University, Columbus, OH, USA.
Heather D'AngeloDepartment of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Meagan M KittDepartment of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Peter M GraceLaboratories of Neuroimmunology, Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nathan D AndersenDepartment of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Shaelyn N SilvermanDepartment of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Kenner C RiceDrug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Linda R WatkinsDepartment of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Steven F MaierDepartment of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Ruth M BarrientosInstitute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA; Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA; Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA; Chronic Brain Injury Program, Discovery Themes Initiative, The Ohio State University, Columbus, OH, USA. Electronic address: ruth.barrientos@osumc.edu.
University of Colorado Boulder · USInstitute for Behavioral Medicine · USNational Institute on Alcohol Abuse and Alcoholism · USThe Ohio State University · USThe University of Texas MD Anderson Cancer Center · US

Funding

Medicinal Chemistry of Drugs Acting on Central and Peripheral Opioid ReceptorsZIADA000527 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI RICE, KENNER · 2009 to 2025
$23.2M
Neuroinflammation, Inflammatory Challenge, and MemoryRF1AG028271 · NIA · UNIVERSITY OF COLORADO · PI BARRIENTOS, RUTH M, MAIER, STEVEN F · 2018 to 2021
$2.4M
NIA NIH HHS RF1 AG028271
6 · The paper itself

Abstract

Postoperative cognitive dysfunction (POCD) is the collection of cognitive impairments, lasting days to months, experienced by individuals following surgery. Persistent POCD is most commonly experienced by older individuals and is associated with a greater vulnerability to developing Alzheimer's disease, but the underlying mechanisms are not known. It is known that laparotomy (exploratory abdominal surgery) in aged rats produces memory impairments for 4 days. Here we report that postsurgical treatment with morphine extends this deficit to at least 2 months while having no effects in the absence of surgery. Indeed, hippocampal-dependent long-term memory was impaired 2, 4, and 8 weeks postsurgery only in aged, morphine-treated rats. Short-term memory remained intact. Morphine is known to have analgesic effects via μ-opioid receptor activation and neuroinflammatory effects through Toll-like receptor 4 activation. Here we demonstrate that persistent memory deficits were mediated independently of the μ-opioid receptor, suggesting that they were evoked through a neuroinflammatory mechanism and unrelated to pain modulation. In support of this, aged, laparotomized, and morphine-treated rats exhibited increased gene expression of various proinflammatory markers (IL-1β, IL-6, TNFα, NLRP3, HMGB1, TLR2, and TLR4) in the hippocampus at the 2-week time point. Furthermore, central blockade of IL-1β signaling with the specific IL-1 receptor antagonist (IL-1RA), at the time of surgery, completely prevented the memory impairment. Finally, synaptophysin and PSD95 gene expression were significantly dysregulated in the hippocampus of aged, laparotomized, morphine-treated rats, suggesting that impaired synaptic structure and/or function may play a key role in this persistent deficit. This instance of long-term memory impairment following surgery closely mirrors the timeline of persistent POCD in humans and may be useful for future treatment discoveries.

Indexed as

AgingAlzheimer DiseaseAnimalsCytokinesGene ExpressionHippocampusInflammation MediatorsLaparotomyMemory DisordersMemory, Long-TermMemory, Short-TermMorphinePostoperative Cognitive ComplicationsRatsReceptors, Opioid, muToll-Like Receptor 4CytokinesInflammation MediatorsMorphineReceptors, Opioid, muToll-Like Receptor 4AgingAlzheimer's diseaseCognitive impairmentHippocampusMorphineNeuroinflammationOpioidsSurgerySynaptic dysfunction

Identifiers

PMID33341652
PMCPMC7870544
OpenAlexW3107726627

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.