ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2024
Activation of LXRs alleviates neuropathic pain-induced cognitive dysfunction by modulation of microglia polarization and synaptic plasticity via PI3K/AKT pathway.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 19 citations in OpenAlex.
- LXR Pathway Activation by T0901317: A Novel Potential Experimental Strategy for ALS-Related Cognitive and Motor Impairments via Suppression of Necroptosis-associated RIPK1/RIPK3/MLKL Markers.Molecular neurobiology · 2026Article
- Targeting druggable kinases in neuropathic pain.npj drug discovery · 2026Review
- Aberrant CX3CL1-CX3CR1 Signaling Reprograms Microglial Exosome Secretion via KIFC2 to Drive Cognitive Impairment in Chronic Pain.International journal of molecular sciences · 2026Article
- Microglia-specific NLRP3 inhibition mitigates hippocampal neuroinflammation and cognitive deficits after hemorrhagic shock with resuscitation.Behavioral and brain functions : BBF · 2026Article
- Schwann Cell Synthesized Cholesterol Orchestrates Peripheral Nerve Regeneration via Structural and IGF1-Dependent Signaling Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nr4a1 regulates microglia overactivation-mediated neuroinflammation to ameliorate cognitive impairment in trigeminal neuralgia rats.The journal of headache and pain · 2026Article
- Hypoactivity of the prelimbic cortex projecting to the lateral entorhinal cortex contributes to neuropathic pain-induced object recognition memory impairment in mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Microglia-derived neuroinflammatory pathways in neuropathic pain.The Korean journal of pain · 2026Review
- CALB2 Overexpression Attenuates Neuropathic Pain by Inhibiting Oxidative Stress and Modulating Microglia M1/M2 Polarization Through Activation of the cAMP/CREB Pathway.Neurochemical research · 2025Article
- Dihydroartemisinin enhances remyelination by switching microglia to the reparative phenotype.Journal of neuroinflammation · 2025Article
- Identification of Potential Intervention Targets Involved in Prior Exercise that Attenuates Peripheral Neuropathic Pain by Integrating Transcriptome and Whole-genome Bisulfite Sequencing Analyses.Molecular neurobiology · 2025Article
- Mechanisms of comorbidity between Alzheimer's disease and pain.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Chronic pain and cognitive dysfunction: clinical manifestations, underlying mechanisms, and emerging therapeutic strategies.Frontiers in neuroscience · 2025Review
- FOXA2/miR-148a-3p/SMURF2 signaling feed-forward loop alleviates spinal cord ischemia-reperfusion injury-induced neuropathic pain by modulating microglia polarization in rats.Frontiers in immunology · 2025Article
- Neurodegenerative diseases and catechins: (-)-epigallocatechin-3-gallate is a modulator of chronic neuroinflammation and oxidative stress.Frontiers in nutrition · 2024Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveCognitive dysfunction is a common comorbidity in patients with chronic pain. Activation of Liver X receptors (LXRs) plays a potential role in improving cognitive disorders in central nervous diseases. In this study, we investigated the role of LXRs in cognitive deficits induced by neuropathic pain.
methodsWe established the spared nerve injury (SNI) model to investigate pain-induced memory dysfunction. Pharmacological activation of LXRs with T0901317 or inhibition with GSK2033 was applied. PI3K inhibitor LY294002 was administered to explore the underlying mechanism of LXRs. Changes in neuroinflammation, microglia polarization, and synaptic plasticity were assessed using biochemical technologies.
resultsWe found that SNI-induced cognitive impairment was associated with reduced LXRβ expression, increased M1-phenotype microglia, decreased synaptic proteins, and inhibition of PI3K/AKT signaling pathway in the hippocampus. Activation of LXRs using T0901317 effectively alleviated SNI-induced cognitive impairment. Additionally, T0901317 promoted the polarization of microglia from M1 to M2, reduced pro-inflammatory cytokines, and upregulated synaptic proteins in the hippocampus. However, administration of GSK2033 or LY294002 abolished these protective effects of T0901317 in SNI mice.
conclusionsLXRs activation alleviates neuropathic pain-induced cognitive impairment by modulating microglia polarization, neuroinflammation, and synaptic plasticity, at least partly via activation of PI3K/AKT signaling in the hippocampus. LXRs may be promising targets for addressing pain-related cognitive deficits.
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