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

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dc.contributor.authorPiao, Yibo
dc.contributor.authorGwon, Do Hyeong
dc.contributor.authorKang, Dong-Wook
dc.contributor.authorHwang, Tae Woong
dc.contributor.authorShin, Nara
dc.contributor.authorKwon, Hyeok Hee
dc.contributor.authorShin, Hyo Jung
dc.contributor.authorYin, Yuhua
dc.contributor.authorKim, Jwa-Jin
dc.contributor.authorHong, Jinpyo
dc.contributor.authorKim, Hyun-Woo
dc.contributor.authorKim, Yonghyun
dc.contributor.authorKim, Sang Ryong
dc.contributor.authorOh, Sang-Ha
dc.contributor.authorKim, Dong Woon
dc.contributor.otherChungnam National University
dc.contributor.otherChungnam National University Hospital
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherKyungpook National University
dc.date.accessioned2023-09-28T22:05:14Z
dc.date.available2023-09-28T22:05:14Z
dc.date.issued2018
dc.description.abstractNeuropathic 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.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationPiao, Y., Gwon, D. H., Kang, D.-W., Hwang, T. W., Shin, N., Kwon, H. H., Shin, H. J., Yin, Y., Kim, J.-J., Hong, J., Kim, H.-W., Kim, Y., Kim, S. R., Oh, S.-H., & Kim, D. W. (2018). TLR4-mediated autophagic impairment contributes to neuropathic pain in chronic constriction injury mice. In Molecular Brain (Vol. 11, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/s13041-018-0354-y
dc.identifier.doi10.1186/s13041-018-0354-y
dc.identifier.orcidhttps://orcid.org/0000-0001-7691-1394
dc.identifier.orcidhttps://orcid.org/0000-0001-6344-1258
dc.identifier.orcidhttps://orcid.org/0000-0003-0299-1613
dc.identifier.orcidhttps://orcid.org/0000-0002-8796-8967
dc.identifier.orcidhttps://orcid.org/0000-0003-3734-5005
dc.identifier.urihttps://ir.ua.edu/handle/123456789/12324
dc.languageEnglish
dc.language.isoen_US
dc.publisherBiomed Central
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectTLR4
dc.subjectAutophagy
dc.subjectGlia
dc.subjectNeuropathic pain
dc.subjectCCI
dc.subjectMECHANICAL ALLODYNIA
dc.subjectMOLECULAR MACHINERY
dc.subjectSPINAL MICROGLIA
dc.subjectINNATE IMMUNITY
dc.subjectRECEPTOR 4
dc.subjectCNS
dc.subjectACTIVATION
dc.subjectMODEL
dc.subjectRAT
dc.subjectMITOPHAGY
dc.subjectNeurosciences
dc.titleTLR4-mediated autophagic impairment contributes to neuropathic pain in chronic constriction injury miceen_US
dc.typeArticle
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