ArticleSignal transduction and targeted therapy2023
Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- mmVelo: a deep generative model for estimating cell state-dependent dynamics across multiple modalities.Bioinformatics (Oxford, England) · 2026Article
- The neuroimmune system and cognition.Nature immunology · 2026Review
- Prelimbic cortex layer 5 GABAergic neurons mediate chronic pain and memory impairment by regulating excitatory/inhibitory imbalance.The journal of headache and pain · 2026Article
- Review
- Nr4a1 regulates microglia overactivation-mediated neuroinflammation to ameliorate cognitive impairment in trigeminal neuralgia rats.The journal of headache and pain · 2026Article
- Subtype-Specific Roles of Anterior Cingulate Cortex Neurons in Pain-Induced Social Deficits in Mice.Theranostics · 2026Article
- Sex-specific lateralization of the effects of exogenously-induced neuroimmune activation in the amygdala on pain-like behaviors.Frontiers in pharmacology · 2026Article
- The Role of Toll-like Receptor 3 Signaling in Cognitive Impairment Induced by Propofol Addiction.Molecular neurobiology · 2025Article
- Hippocampal Extracellular Matrix Protein Laminin β1 Regulates Neuropathic Pain and Pain-Related Cognitive Impairment.Neuroscience bulletin · 2025Article
- Late-Stage Activation of Toll-like receptor 3 Alleviates Cognitive Impairment and Neuropathology in an Alzheimer's Disease Mouse Model.Molecular neurobiology · 2025Article
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Review
- Astrocyte-derived extracellular vesicular NFIA mediates obesity-associated cognitive impairment.Journal of neuroinflammation · 2025Article
- ETS2 aggravate allergic airway inflammation by regulating ANT2-mediated cytosolic mitochondrial DsRNA levels.Respiratory research · 2025Article
- Neutrophil extracellular trap-derived double-stranded RNA aggravates PANoptosis in renal ischemia reperfusion injury.Cell communication and signaling : CCS · 2025Article
- Mechanisms of comorbidity between Alzheimer's disease and pain.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Toll-like receptor-mediated immune imbalance in asthma: controversies, breakthroughs, and future directions.Frontiers in immunology · 2025Review
- Chronic pain and cognitive dysfunction: clinical manifestations, underlying mechanisms, and emerging therapeutic strategies.Frontiers in neuroscience · 2025Review
- Targeting exosomal double-stranded RNA-TLR3 signaling pathway attenuates morphine tolerance and hyperalgesia.Cell reports. Medicine · 2024Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic pain is often associated with cognitive decline, which could influence the quality of the patient's life. Recent studies have suggested that Toll-like receptor 3 (TLR3) is crucial for memory and learning. Nonetheless, the contribution of TLR3 to the pathogenesis of cognitive decline after chronic pain remains unclear. The level of TLR3 in hippocampal neurons increased in the chronic constriction injury (CCI) group than in the sham group in this study. Importantly, compared to the wild-type (WT) mice, TLR3 knockout (KO) mice and TLR3-specific neuronal knockdown mice both displayed improved cognitive function, reduced levels of inflammatory cytokines and neuronal apoptosis and attenuated injury to hippocampal neuroplasticity. Notably, extracellular RNAs (exRNAs), specifically double-stranded RNAs (dsRNAs), were increased in the sciatic nerve, serum, and hippocampus after CCI. The co-localization of dsRNA with TLR3 was also increased in hippocampal neurons. And the administration of poly (I:C), a dsRNA analog, elevated the levels of dsRNAs and TLR3 in the hippocampus, exacerbating hippocampus-dependent memory. In additon, the dsRNA/TLR3 inhibitor improved cognitive function after CCI. Together, our findings suggested that exRNAs, particularly dsRNAs, that were present in the condition of chronic neuropathic pain, activated TLR3, initiated downstream inflammatory and apoptotic signaling, caused damage to synaptic plasticity, and contributed to the etiology of cognitive impairment after chronic neuropathic pain.
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