I am a
Home I AM A Search Login

Papers of the Week

Papers: 3 Sep 2022 - 9 Sep 2022


Animal Studies, Pharmacology/Drug Development

2022 Sep 02

Mol Psychiatry

Editor's Pick

Chronic pain causes Tau-mediated hippocampal pathology and memory deficits.


Guerreiro SR, Guimarães MR, Silva JM, Dioli C, Vamvaka-Iakovou A, Sousa R, Gomes P, Megalokonomou A, Campos-Marques C, Cunha A M, Almeida A, Sousa N, Leite-Almeida H, Sotiropoulos I
Mol Psychiatry. 2022 Sep 02.
PMID: 36056171.


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.