LRP1-mediated p-tau propagation contributes to cognitive impairment after chronic neuropathic pain in rats

• Published in: Neuroscience research Vol. 212; pp. 84 - 96
• Main Authors: Ning, Youzhi, Zhang, Yue, Jiang, Tao, Feng, Jianguo, Zhan, Jian, Ou, Cehua, Wang, Lu
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.03.2025; Elsevier
• Subjects: Animals; Chronic neuropathic pain; Chronic Pain - metabolism; Cognitive Dysfunction - etiology; Cognitive Dysfunction - metabolism; Cognitive impairment; Disease Models, Animal; Hippocampus - metabolism; Low Density Lipoprotein Receptor-Related Protein-1 - metabolism; LRP1; Male; Neuralgia - metabolism; P-tau; Phosphorylation; Rats; Rats, Sprague-Dawley; tau Proteins - metabolism; Trigeminal neuralgia; Trigeminal Neuralgia - complications; Trigeminal Neuralgia - metabolism; Chronic neuropathic pain; Trigeminal neuralgia; LRP1; P-tau; Cognitive impairment
• ISSN: 0168-0102; 1872-8111; 1872-8111
• DOI: 10.1016/j.neures.2024.12.005

Trigeminal neuralgia (TN) is a prevalent chronic neuropathic pain syndrome characterized by severe pain, often accompanied by cognitive dysfunction and cerebral degeneration. However, its mechanisms remain poorly understood. Hyperphosphorylation of tau protein (p-tau) is often seen in neurodegenerative disorders such as Alzheimer's disease (AD). LRP1 expression on brain neurons and microglial cells is believed to facilitate the propagation of p-tau. We established a TN rat model via infraorbital nerve chronic constrictive injury (ION-CCI). Once the model was established, we investigated the association between p-tau and cognitive impairment in TN rats by evaluating behavioral and degenerative markers. During the initial phase, we noted an increase in p-tau level in the prefrontal cortex and hippocampal tissues of TN rats. The accompanied impaired learning and memory abilities suggested cognitive dysfunction. Blocking p-tau synthesis by orally administering a protein phosphatase and by injecting adenoviral vectors targeting LRP1 into the lateral ventricle of rats ameliorated cognitive impairment. This suggests that cognitive decline in TN rats is linked to elevated p-tau levels. Our findings show that LRP1-mediated p-tau propagation may drive cognitive impairment associated with neuropathic pain in TN rats. •LRP1-mediated p-tau propagation drives cognitive impairment in TN rat model.•Chronic neuropathic pain leads to elevated p-tau in prefrontal cortex and hippocampus.•Blocking p-tau synthesis and LRP1 reduces cognitive dysfunction in TN rats.•Study links tau hyperphosphorylation to cognitive decline in chronic neuropathic pain.