TLR4-mediated autophagic impairment contributes to neuropathic pain in chronic constriction injury miceстатья из журнала
Аннотация: 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.
Год издания: 2018
Авторы: Yibo Piao, Do Hyeong Gwon, Dong‐Wook Kang, Tae Woong Hwang, Nara Shin, Hyeok Hee Kwon, Hyo Jung Shin, Yuhua Yin, Jwa-Jin Kim, Jinpyo Hong, Hyun‐Woo Kim, Yonghyun Kim, Sang Ryong Kim, Sang‐Ha Oh, Dong Woon Kim
Издательство: BioMed Central
Источник: Molecular Brain
Ключевые слова: Pain Mechanisms and Treatments, Botulinum Toxin and Related Neurological Disorders, Nerve injury and regeneration
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Molecular Brain (HTML)
DOAJ (DOAJ: Directory of Open Access Journals) (HTML)
PubMed Central (HTML)
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