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

Autor: Piao Y; Department of Plastic and Reconstructive Surgery, Department of Pediatrics, Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea., Gwon DH; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea., Kang DW; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea., Hwang TW; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea., Shin N; Department of Plastic and Reconstructive Surgery, Department of Pediatrics, Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea.; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea., Kwon HH; Department of Plastic and Reconstructive Surgery, Department of Pediatrics, Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea.; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea., Shin HJ; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea., Yin Y; Department of Plastic and Reconstructive Surgery, Department of Pediatrics, Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea.; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea., Kim JJ; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea.; LES Corporation Inc., Gung-Dong 465-16, Yuseong-Gu, Daejeon, 305-335, Republic of Korea., Hong J; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea., Kim HW; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea., Kim Y; Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, 35487, USA., Kim SR; School of Life Sciences, BK21 plus KNU Creative BioResearch Group, Institute of Life Science & Biotechnology, Kyungpook National University, Daegu, 41566, South Korea., Oh SH; Department of Plastic and Reconstructive Surgery, Department of Pediatrics, Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea. djplastic@cnu.ac.kr.; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. djplastic@cnu.ac.kr., Kim DW; Department of Medical Science, Department of Physiology, Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. visnu528@cnu.ac.kr.
Jazyk: angličtina
Zdroj: Molecular brain [Mol Brain] 2018 Feb 27; Vol. 11 (1), pp. 11. Date of Electronic Publication: 2018 Feb 27.
DOI: 10.1186/s13041-018-0354-y
Abstrakt: 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 not microglia, of WT-Ipsi group compared with the WT-Contra group. The level of PINK1, a marker for mitophagy was increased in the neurons of WT, but not in TLR4 KO mice. Together, these results show that TLR4-mediated p62 autophagic impairment plays an important role in the occurrence and development of neuropathic pain. And what is more, microglial TLR4-mediated microglial activation might be indirectly coupled to neuronal autophage.
Databáze: MEDLINE
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