ArticleJournal of neuroinflammation2020
Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 214 citations in OpenAlex.
- Microglia and neuroinflammation: An in-depth analysis from functional diversity to disease mechanisms.Clinical and translational medicine · 2026Review
- A2 astrocyte polarization mediates ketogenic diet protection of blood-central nervous system barriers in experimental autoimmune encephalomyelitis.Neural regeneration research · 2026Article
- Oligodendrocyte and Astrocyte Dynamics During Short-Term Cuprizone Treatment.Brain and behavior · 2026Article
- Neurobehavioral Effects of Two Distinct Anti-Inflammatory Drugs in a Two-Week Chronic Stress Model in Zebrafish.Brain sciences · 2026Article
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Network Pharmacology and Experimental Validation Unravel How Puerarin Improves Chronic Postoperative Pain.Molecular biotechnology · 2026Article
- Mechanism prediction of Wenjing Tongluo Powder for post-laparoscopic shoulder pain: A network pharmacology study.Medicine · 2026Article
- CAR Treg therapies for neurodegenerative diseases.iScience · 2026Review
- TMEM251 loss-induced autophagy dysfunction in the anterior cingulate cortex contributes to chronic postoperative pain.EMBO reports · 2026Article
- Microglia-derived neuroinflammatory pathways in neuropathic pain.The Korean journal of pain · 2026Review
- Profibrotic macrophage-derived CXCL4 promotes pericyte-to-myofibroblast transition after spinal cord injury.Journal of orthopaedic translation · 2026Article
- Time-dependent histological characterization of amyloid-β induced cholinergic and glial alterations and their modulation by dehydroepiandrosterone sulfate (DHEAS).Frontiers in endocrinology · 2026Article
- The neurons in NAc core receiving ACC excitatory afferents contribute to chronic postoperative pain.iScience · 2025Article
- Amelioration of Alzheimer's Disease Pathology in Zebrafish by Photobiomodulation.Biomedicines · 2025Article
- Fibroblast Growth Factor 8 Suppresses Neurotoxic Astrocytes and Alleviates Neuropathic Pain via Spinal FGFR3 Signaling.Neuroscience bulletin · 2025Article
- A1-Reactive Astrocytes in the Posterior Part of Paraventricular Thalamic Nucleus Are Involved in Pain Modulation in Mice.Molecular neurobiology · 2025Article
- Increased reactive astrocytes in hippocampal CA1 region mediated by decreased CXCR7 is involved in postoperative cognitive dysfunction in aged mice.Cell biology and toxicology · 2025Article
- Neobaicalein Alleviates Retinal Damage via Microglia-Mediated Astrocyte Phenotypic Transformation.Applied biochemistry and biotechnology · 2025Article
- Complex Genetics and Regulatory Drivers of Hypermobile Ehlers-Danlos Syndrome: Insights from Genome-Wide Association Study Meta-analysis.medRxiv : the preprint server for health sciences · 2025Article
- Astrocyte Lipid Droplet Dynamics Orchestrate Neurological Disorders and Therapeutic Horizons.Small science · 2025Review
53 more citing papers are in PubMed but not listed here.
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9 authors at 2 institutions in 1 country.
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Abstract
backgroundActivated astrocytes play important roles in chronic post-surgical pain (CPSP). Recent studies have shown reactive astrocytes are classified into A1 and A2 phenotypes, but their precise roles in CPSP remain unknown. In this study, we investigated the roles of spinal cord A1 and A2 astrocytes and related mechanisms in CPSP.
methodsWe used a skin/muscle incision and retraction (SMIR) model to establish a rat CPSP model. Microglia, CXCR7, and the phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways were regulated by intrathecal injections of minocycline (a non-specific microglial inhibitor), AMD3100 (a CXCR7 agonist), and LY294002 (a specific PI3K inhibitor), respectively. Mechanical allodynia was detected with von Frey filaments. The changes in microglia, A1 astrocytes, A2 astrocytes, CXCR7, and PI3K/Akt signaling pathways were examined by enzyme-linked immunosorbent assay (ELISA), western blot, and immunofluorescence.
resultsMicroglia were found to be activated, with an increase in interleukin-1 alpha (IL-1α), tumor necrosis factor alpha (TNFα), and complement component 1q (C1q) in the spinal cord at an early stage after SMIR. On day 14 after SMIR, spinal cord astrocytes were also activated; these were mainly of the A1 phenotype and less of the A2 phenotype. Intrathecal injection of minocycline relieved SMIR-induced mechanical allodynia and reverted the ratio of A1/A2 reactive astrocytes. The expression of CXCR7 and PI3K/Akt signaling was decreased after SMIR, while they were increased after treatment with minocycline. Furthermore, intrathecal injection of AMD3100 also relieved SMIR-induced mechanical allodynia, reverted the ratio of A1/A2 reactive astrocytes, and activated the PI3K/Akt signaling pathway, similar to the effects produced by minocycline. However, intrathecal injection of AMD3100 did not increase the analgesic effect of minocycline. Last, LY294002 inhibited the analgesic effect and A1/A2 transformation induced by minocycline and AMD3100 after SMIR.
conclusionOur results indicated that microglia induce the transformation of astrocytes to the A1 phenotype in the spinal cord via downregulation of the CXCR7/PI3K/Akt signaling pathway during CPSP. Reverting A1 reactive astrocytes to A2 may represent a new strategy for preventing CPSP.
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