TLR4-mediated autophagic impairment contributes to neuropathic pain in chronic constriction injury mice

Molecular Brain
Yibo PiaoDong Woon Kim

Abstract

Neuropathic pain is a complex, chronic pain state characterized by hyperalgesia, allodynia, and spontaneous pain. Accumulating evidence has indicated that the microglial Toll-like receptor 4 (TLR4) and autophagy are implicated in neurodegenerative diseases, but their relationship and role in neuropathic pain remain unclear. In this study, we examined TLR4 and its association with autophagic activity using a chronic constriction injury (CCI)-induced neuropathic pain model in wild-type (WT) and TLR4-knockout (KO) mice. The mice were assigned into four groups: WT-Contralateral (Contra), WT-Ipsilateral (Ipsi), TLR4 KO-Contra, and TLR4 KO-Ipsi. Behavioral and mechanical allodynia tests and biochemical analysis of spinal cord tissue were conducted following CCI to the sciatic nerve. Compared with the Contra group, mechanical allodynia in both the WT- and TLR4 KO-Ipsi groups was significantly increased, and a marked decrease of allodynia was observed in the TLR4 KO-Ipsi group. Although glial cells were upregulated in the WT-Ipsi group, no significant change was observed in the TLR4 KO groups. Moreover, protein expression and immunoreactive cell regulation of autophagy (Beclin 1, p62) were significantly increased in the neurons, but no...Continue Reading

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Citations

Oct 26, 2018·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Yuhua YinDong Woon Kim
Jun 28, 2020·Phytotherapy Research : PTR·Mahboobeh Ghasemzadeh RahbardarHossein Hosseinzadeh
Jul 18, 2018·International Journal of Molecular Medicine·Hongguang ChenYonghao Yu
Jan 28, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·C LeiguardaPablo R Brumovsky
Feb 6, 2021·Neuroscience and Biobehavioral Reviews·Deborah ChiabrandoEmanuela Tolosano
Jun 27, 2021·Brain, Behavior, and Immunity·Thomas A Szabo-PardiMichael D Burton

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

CatWalk
ImageJ
CatWalk XT
Graph Pad
Image J
Prism

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