ArticleJournal of neuroinflammation2016
Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 123 citations in OpenAlex.
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Arachidonic acid metabolism in spinal cord injury.Journal of advanced research · 2026Review
- Spinal cord stimulation: An emerging strategy for chronic pain relief after spinal cord injury.Neural regeneration research · 2026Article
- Lipoxin A4 and Resolvin D1 Preserve Neural Inductive Capacity of Dental Pulp Stem Cells Cultured Under Inflammatory Conditions.Cell biology international · 2026Article
- Lipoxin B4 Mitigates TRPV4-Activated Müller Cell Gliosis During Ocular Hypertension.Investigative ophthalmology & visual science · 2026Article
- Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosis.The Journal of clinical investigation · 2026Article
- Dysregulated Resolution of Inflammation After Respiratory Viral Infections: Molecular Pathways Linking Neuroinflammation to Post-Viral Neuropathic Pain-A Narrative Review.International journal of molecular sciences · 2025Review
- Sensory Deficits in Mice with Lateral Spinal Cord Hemisection Mimic the Brown-Séquard Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Lipoxin BbioRxiv : the preprint server for biology · 2025Article
- Lipoxins as Modulators of Diseases.Cells · 2025Review
- Dysregulation of Arachidonic Acid Metabolism Drives Inflammatory Lipid Production in Localized Provoked Vulvodynia.Nutrients · 2025Article
- Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury.Stem cell research & therapy · 2025Article
- Anti-arthritis Effect of Anti-chitinase-3-like 1 Antibody Through Inhibition of MMP3.Immune network · 2025Article
- Review
- Targeting formyl peptide receptor 2 to suppress neuroinflammation in neuromyelitis optica spectrum disorder.Theranostics · 2025Article
- The mechanisms of specialized pro-resolving mediators in pain relief: neuro-immune and neuroglial regulations.Frontiers in immunology · 2025Review
- Neuropathic Pain Induced by Spinal Cord Injury from the Glia Perspective and Its Treatment.Cellular and molecular neurobiology · 2024Review
- Regulation of disease-associated microglia in the optic nerve by lipoxin BMolecular neurodegeneration · 2024Article
- Regulation of Diseases-Associated Microglia in the Optic Nerve by Lipoxin BbioRxiv : the preprint server for biology · 2024Article
- Exploring PGE2 and LXA4 Levels in Migraine Patients: The Potential of LXA4-Based Therapies.Diagnostics (Basel, Switzerland) · 2024Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundSpinal cord injury (SCI) is a severe neurological disorder with many disabling consequences, including persistent neuropathic pain, which develops in about 40 % of SCI patients and is induced and sustained by excessive and uncontrolled spinal neuroinflammation. Here, we have evaluated the effects of lipoxin A4 (LXA4), a member of a unique class of endogenous lipid mediators with both anti-inflammatory and analgesic properties, on spinal neuroinflammation and chronic pain in an experimental model of SCI.
methodsSpinal hemisection at T10 was carried out in adult male CD1 mice and Wistar rats. To test if LXA4 can reduce neuroinflammation and neuropathic pain, each animal received two intrathecal injections of LXA4 (300 pmol) or vehicle at 4 and 24 h after SCI. Sensitivity to mechanical stimulation of the hind paws was evaluated using von Frey monofilaments, and neuroinflammation was tested by measuring the mRNA and/or protein expression levels of glial markers and cytokines in the spinal cord samples after SCI. Also, microglia cultures prepared from murine cortical tissue were used to assess the direct effects of LXA4 on microglial activation and release of pro-inflammatory TNF-α.
resultsLXA4 treatment caused significant reductions in the intensity of mechanical pain hypersensitivity and spinal expression levels of microglial markers and pro-inflammatory cytokines induced by SCI, when compared to rodents receiving control vehicle injections. Notably, the increased expressions of the microglial marker IBA-1 and of the pro-inflammatory cytokine TNF-α were the most affected by the LXA4 treatment. Furthermore, cortical microglial cultures expressed ALX/FPR2 receptors for LXA4 and displayed potentially anti-inflammatory responses upon challenge with LXA4.
conclusionsCollectively, our results suggest that LXA4 can effectively modulate microglial activation and TNF-α release through ALX/FPR2 receptors, ultimately reducing neuropathic pain in rodents after spinal cord hemisection. The dual anti-inflammatory and analgesic properties of LXA4, allied to its endogenous nature and safety profile, may render this lipid mediator as new therapeutic approach for treating various neuroinflammatory disorders and chronic pain with only limited side effects.
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