ArticleCNS neuroscience & therapeutics2025
C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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.
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.
Who cites it
9 citing papers in PubMed.
- C3aR inhibition alleviates cerebral ischemia-reperfusion injury via STING-mediated ferroptosis through SLC7A11/GPX4.iScience · 2026Article
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Pathological Roles of Astrocytes in Traumatic Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Integrative analysis via bioinformatics and machine learning identifies SERPING1 as a biomarker candidate for major depressive disorder.BMC psychiatry · 2026Article
- Integrated transcriptomic and proteomic profiling reveals C3-associated hippocampal neuroimmune remodeling in sodium bicarbonate-treated sepsis-associated encephalopathy.Frontiers in neuroscience · 2026Article
- Synaptic-immune interactions in neuropathic pain: complement-mediated remodeling of spinal dorsal horn microcircuits.Frontiers in cell and developmental biology · 2026Review
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Complement C1q is associated with neuroinflammation and mediates the association between amyloid-β and tau pathology in Alzheimer's disease.Translational psychiatry · 2025Article
- The therapeutic potential of phytochemicals in morphine tolerance: targeting microglia-mediated neuroinflammation.Frontiers in pharmacology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
aimsCommunication within glial cells acts as a pivotal intermediary factor in modulating neuroimmune pathology. Meanwhile, an increasing awareness has emerged regarding the detrimental role of glial cells and neuroinflammation in morphine tolerance (MT). This study investigated the influence of crosstalk between astrocyte and microglia on the evolution of morphine tolerance.
methodsSprague-Dawley rats were intrathecally treated with morphine twice daily for 9 days to establish morphine-tolerant rat model. Tail-flick latency test was performed to identify the analgesic effect of morphine. The role of microglia, astrocyte and C3-C3aR axis in morphine tolerance were elucidated by real-time quantitative polymerase chain reaction, Western blot, and immunofluorescence.
resultsChronic morphine treatment notably promoted the activation of microglia, upregulated the production of proinflammatory mediators (interleukin-1 alpha (IL-1α), tumor necrosis factor alpha (TNFα), and complement component 1q (C1q)). Simultaneously, it programed astrocytes to a pro-inflammatory phenotype (A1), which mainly expresses complement 3 (C3) and serping1. PLX3397 (a colony-stimulating factor 1 receptor (CSF1R) inhibitor), Compstain (a C3 inhibitor) and SB290157(a C3aR antagonist) could reverse the above pathological process and alleviate morphine tolerance to different extents.
conclusionOur findings identify C3-C3aR axis as an amplifier of microglia-astrocyte crosstalk, neuroinflammation and a node for therapeutic intervention in morphine tolerance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.