Evidence map›Paper›PMID 40447886›Full record

ArticleJournal of neurovirology2025

Differential effects of fentanyl compared to morphine on neuroinflammatory signaling in the brain in EcoHIV-infected mice.

Kara Rademeyer, Austin M Jones, Emily A Miller, Daniel Conway, Joseph L McClay, Kurt F Hauser, MaryPeace McRae

Abstract readComparative Study
In one paragraph

Article in Journal of neurovirology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

7 authors.

Kara RademeyerDepartment of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, 23298, U.S.A.
Austin M JonesDepartment of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, 23298, U.S.A.
Emily A MillerDepartment of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, 23298, U.S.A.
Daniel ConwayDepartment of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, U.S.A.
Joseph L McClayDepartment of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, 23298, U.S.A.
Kurt F HauserDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, U.S.A.
MaryPeace McRaeDepartment of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, 23298, U.S.A.. mpmcrae@vcu.edu.

Funding

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Cell junction and nuclear forces as mediators of epithelial cell homeostasisR35GM119617 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI Daniel E Conway · 2016 to 2026
$4.5M
Mechanism of Cannabidiol Effects on HIV Expression, Neuroinflammation, and HIV Cognitive Disease in Chronically-infected Immunocompetent MiceR01DA052844 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BORJABAD, ALEJANDRA, KELSCHENBACH, JENNIFER L · 2020 to 2024
$3.6M
Opioid- and HIV-mediated effects on the integrity of the blood-brain barrier, on immune cell recruitment, and on antiretroviral penetration into thebrainR01DA053153 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI MCRAE, MARY PEACE · 2021 to 2025
$2.5M
Routes to Enhanced HIV Neuropathogenesis Through Expression of Subclinical Levels of Endogenous Amyloid-BetaR01NS119438 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ARANCIO, OTTAVIO, VOLSKY, DAVID J · 2025 to 2025
$828k
NIAID NIH HHS P30 AI050410NIDA NIH HHS R01 DA052844NIDA NIH HHS R01 DA053153NIGMS NIH HHS R35 GM119617NINDS NIH HHS R01 NS119438
6 · The paper itself

Abstract

HIV-associated neurocognitive disorders (HAND) pose significant challenges, particularly in individuals with comorbid opioid use disorder (OUD). Fentanyl, a potent synthetic opioid, is a leading contributor to opioid-related fatalities, yet its effects in the context of HIV remain poorly understood. This study investigated the differential impacts of fentanyl and morphine on neuroinflammatory signaling, blood-brain barrier (BBB) integrity, and antiretroviral (ARV) brain accumulation in EcoHIV-infected mice. C57BL/6 mice were assigned to morphine, fentanyl, or saline treatment groups, with or without EcoHIV infection. Tight junction proteins claudin-5 and ZO-1 were measured in striatum and hippocampus via ELISA, while proinflammatory chemokines were analyzed by multiplex assay. In EcoHIV-infected mice, both opioids significantly increased CCL2, CCL4, CCL5, and CCL11 concentrations in the striatum, with fentanyl causing greater increases in CCL2 than morphine. Additionally, fentanyl, but not morphine, significantly decreased CCL3 concentrations in the striatum. Principal component analysis revealed distinct treatment-specific patterns within the striatum, underscoring opioid-specific differences. Tight junction protein expression data demonstrate opioid-specific, sex-specific, and region-specific effects on the key BBB proteins, ZO-1 and claudin-5. Both opioids also reduced ARV brain concentrations in infected mice, with region- and opioid-specific effects. Fentanyl decreased dolutegravir in the hippocampus, while morphine decreased abacavir in both regions. These findings demonstrate that fentanyl and morphine exposure in the context of HIV produce distinct impacts on neuroinflammatory response, BBB integrity, and ARV brain exposure. Understanding these opioid-specific effects is critical for improving clinical outcomes and treatment strategies for individuals with HIV and OUD.

Indexed as

AIDS Dementia ComplexAnalgesics, OpioidFentanylMorphineNeuroinflammatory DiseasesAnimalsBlood-Brain BarrierBrainClaudin-5Corpus StriatumDisease Models, AnimalFemaleHippocampusHIV-1MaleMiceAnalgesics, OpioidClaudin-5Cldn5 protein, mouseFentanylMorphineTjp1 protein, mouseZonula Occludens-1 ProteinBlood–brain barrierChemokinesEcoHIVFentanylInflammationMorphineOpioid abuse

Identifiers

PMID40447886
PMCPMC12356723

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.