ArticleMolecular psychiatry2022
Chronic pain causes Tau-mediated hippocampal pathology and memory deficits.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Regional homogeneity alterations reflect pain and emotional dysregulation in adenomyosis.Annals of medicine · 2026Article
- Association of chronic pain and analgesic use with the risks of Parkinson's and Alzheimer's disease.GeroScience · 2026Article
- Chronic ocular pain is associated with smaller selective hippocampal subfield in highly symptomatic patients.The journal of pain · 2026Article
- Chronic pain as a risk factor for Alzheimer's disease pathology: a longitudinal ADNI study.Alzheimer's research & therapy · 2026Article
- Beyond microtubule regulation: the multifaceted roles of tau in neuronal function and dysfunction.Translational psychiatry · 2026Review
- Therapeutic relevance of an EU-GMP certifiedFrontiers in pharmacology · 2026Article
- The effect of lateralization bias of pain on pain, anxiety and cognition in mice.Experimental brain research · 2025Article
- Synaptic Dysfunction in the Anterior Cingulate Cortex Underlies Pain-Anxiety Comorbidity in a Mandibular Asymmetry Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hippocampal Extracellular Matrix Protein Laminin β1 Regulates Neuropathic Pain and Pain-Related Cognitive Impairment.Neuroscience bulletin · 2025Article
- Longitudinal MRI identifies associations between cognitive decline, inflammatory markers, and hippocampal subregion volumes in individuals with knee osteoarthritis.Communications medicine · 2025Article
- Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases.Current issues in molecular biology · 2025Review
- Elevated plasma Tau-PT217 linked to decreased hippocampal functional connectivity in patients with knee osteoarthritis.Brain research · 2025Article
- PSD-95 Protein: A Promising Therapeutic Target in Chronic Pain.Molecular neurobiology · 2025Review
- Mechanisms of comorbidity between Alzheimer's disease and pain.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease-A Review.Journal of biochemical and molecular toxicology · 2025Review
- Multisite chronic pain: association with cognitive decline and post-mortem Alzheimer's biomarkers.Brain communications · 2025Article
- Characterization of alterations in spontaneous behaviors in a rat model of neuropathic pain - new outcome measures for pain evaluation?Frontiers in behavioral neuroscience · 2025Article
- Long-term gabapentin treatment impairs cognitive function in aged mice via tau hyperphosphorylation.Frontiers in pharmacology · 2025Article
- Elevated C-Reactive Protein in Older Men With Chronic Pain: Association With Plasma Amyloid Levels and Hippocampal Volume.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Chronic Pain-Related Cognitive Deficits: Preclinical Insights into Molecular, Cellular, and Circuit Mechanisms.Molecular neurobiology · 2024Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Persistent pain has been recently suggested as a risk factor for dementia. Indeed, chronic pain is frequently accompanied by maladaptive brain plasticity and cognitive deficits whose molecular underpinnings are poorly understood. Despite the emerging role of Tau as a key regulator of neuronal plasticity and pathology in diverse brain disorders, the role of Tau has never been studied in the context of chronic pain. Using a peripheral (sciatic) neuropathy to model chronic pain in mice-spared nerve injury (SNI) for 4 months-in wildtype as well as P301L-Tau transgenic mice, we hereby demonstrate that SNI triggers AD-related neuropathology characterized by Tau hyperphosphorylation, accumulation, and aggregation in hippocampus followed by neuronal atrophy and memory deficits. Molecular analysis suggests that SNI inhibits autophagy and reduces levels of the Rab35, a regulator of Tau degradation while overexpression of Rab35 or treatment with the analgesic drug gabapentin reverted the above molecular changes leading to neurostructural and memory recovery. Interestingly, genetic ablation of Tau blocks the establishment of SNI-induced hippocampal morphofunctional deficits supporting the mediating role of Tau in SNI-evoked hippocampal pathology and memory impairment. These findings reveal that exposure to chronic pain triggers Tau-related neuropathology and may be relevant for understanding how chronic pain precipitates memory loss leading to dementia.
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