RETRACTED: Analgesic effects of TLR4/NF-κB signaling pathway inhibition on chronic neuropathic pain in rats following chronic constriction injury of the sciatic nerve

Xu, Longhe; Liu, Yaobo; Sun, Yuhui; Li, Hao; Mi, Weidong; Jiang, Yong

doi:10.1016/j.biopha.2018.07.116

Cited by 40 publications

(36 citation statements)

References 35 publications

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“…LN also supressed IL-1β-induced upregulation of NGF, a neurotrophic factor regulated by NF-κB activation. Furthermore, since NF-κB signalling has been associated with pain (Ahmed et al, 2019;Cao et al, 2019;Xu et al, 2018) and LN suppressed the upregulation of neurotrophins (Noorwali et al, 2012), a von Frey test was performed to determine whether LN could affect nociception in a PMM mouse model of knee OA. In vivo studies demonstrated that a single intra-articular injection of LN significantly reduced advanced stage of chronic OA pain within 3 h and this reduced pain symptom was sustained over 24 h, suggesting its dual effects: (i) improvement of joint pathology and (ii) rapid pain reduction.…”

Section: Discussionmentioning

confidence: 99%

Link N suppresses interleukin-1β-induced biological effects on human osteoarthritic cartilage

Alaqeel¹,

Mp²,

Lm³

et al. 2020

eCM

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Osteoarthritis (OA) is a disease of diarthrodial joints associated with extracellular matrix proteolytic degradation under inflammatory conditions, pain and disability. Currently, there is no therapy to prevent, reverse or modulate the disease course. The present study aimed at evaluating the regenerative potential of Link N (LN) in human OA cartilage in an inflammatory milieu and determining if it could affect pain-related behaviour in a knee OA mouse injury model. Osteo-chondro OA explants and OA chondrocytes were treated with LN in the presence of interleukin-1β (IL-1β) to simulate an osteoarthritic environment. Quantitative von Frey polymerase chain reaction and Western blotting were performed to determine the effect of LN on matrix protein synthesis, catabolic enzymes, cytokines and nerve growth factor expression. Partial medial meniscectomy (PMM) was performed on the knee of C57BL/6 mice and, 12 weeks post-surgery, mice were given a 5 µg intra-articular injection of LN or phosphate-buffered saline. A von Frey test was conducted over 24 h to measure the mechanical allodynia in the hind paw. LN modulated proteoglycan and collagen synthesis in human OA cartilage through inhibition of IL-1βinduced biological effects. LN also supressed IL-1β-induced upregulation of cartilage-degrading enzymes and inflammatory molecules in OA chondrocytes. Upon investigation of the canonical signalling pathways IL-1β and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), LN resulted to significantly inhibit NF-κB activation in a dose-dependent manner. In addition, LN suppressed mechanical allodynia in an OA PMM mouse model. Results supported the concept that LN administration could have therapeutic potential in OA.

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Section: Discussionmentioning

confidence: 99%

Link N suppresses interleukin-1β-induced biological effects on human osteoarthritic cartilage

Alaqeel¹,

Mp²,

Lm³

et al. 2020

eCM

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“…Furthermore, Dex exerted an anti‐nociceptive effect in a monoarthritic rat model through blockage of the Toll‐like receptor 4 (TLR4)–NF‐κB p65 pathway (Ji et al., 2017). The individual role of TLR4–NF‐κB signalling in promoting the NPP has also been established in rats with chronic constriction injury (CCI) of the sciatic nerve (Xu et al., 2018). The CCI rat model is one of the recognized NPP models; it is stimulated by loose ligations around the sciatic nerve and exhibits resemblances to NPP in humans (Nagakura et al., 2012).…”

Section: Introductionmentioning

confidence: 99%

Analgesic effect of dexmedetomidine in rats after chronic constriction injury by mediating microRNA‐101 expression and the E2F2–TLR4–NF‐κB axis

Zhang

Cui

et al. 2020

Experimental Physiology

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New Findings What is the central question of this study?Dexmedetomidine has a capacity for sedation, anti‐anxiety and analgesia with minimal suppression of respiratory function; what is its role in neuropathic pain and what is the involvement of miRNAs? What is the main finding and its importance?Dexmedetomidine attenuates inflammation and apoptosis and the stimulation of TLR4–NF‐κB signalling in rat spinal cord via miR‐101 overexpression and E2F2 downregulation. Abstract The significant analgesic effect of dexmedetomidine (Dex) has been underscored in neuropathic pain (NPP), but the underlying mechanism remains unclear. This study explored the functional effect of Dex on microRNA (miR)‐101‐regulated E2 promoter binding factor 2 (E2F2) with the engagement of Toll‐like receptor 4 (TLR4)–nuclear factor‐κB (NF‐κB) signalling. Chronic constriction injury (CCI) was performed to generate an NPP rat model. The expression of miR‐101, E2F2 and TLR4–NF‐κB signalling‐relevant proteins was assessed by RT–quantitative PCR, immunoblotting and immunohistochemistry. Inflammatory factors were detected by enzyme‐linked immunosorbent assay. The results showed that Dex increased mechanical withdrawal threshold and thermal latency to withdraw. The expression of interleukin (IL)‐6, IL‐8 and tumour necrosis factor‐α was increased in CCI rats, but these trends were reversed by Dex. In addition, Dex repressed caspase‐9 expression and apoptotic cell numbers in spinal cord tissues in CCI rats. Moreover, the expression of E2F2 was significantly increased, while miR‐101 was diminished in CCI rats, which was reversed by Dex. Furthermore, miR‐101 inhibitor, E2F2 restoration or administration of a TLR4‐specific agonist weakened the effect of Dex. Together, these results suggest that Dex has the capacity to ameliorate NPP by regulating the miR‐101–E2F2–TLR4–NF‐κB axis in rats subjected to CCI.

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“…Previous studies demonstrated that HCK could mediate TLR4-induced proinflammatory mediator production via AP-1 [ 38 ]. TLR4, a specific pattern recognition receptor expressed on the microglia surface, was reported to play an important role during the pathological process of neuropathic pain [ 39 , 40 ]. Therefore, it is reasonable to speculate that HCK is associated with the generation of neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis of Neuroimmune Mechanism of Neuropathic Pain

Hao

Liu

et al. 2020

BioMed Research International

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Background. Neuropathic pain (NP) is a devastating complication following nerve injury, and it can be alleviated by regulating neuroimmune direction. We aimed to explore the neuroimmune mechanism and identify some new diagnostic or therapeutic targets for NP treatment via bioinformatic analysis. Methods. The microarray GSE18803 was downloaded and analyzed using R. The Venn diagram was drawn to find neuroimmune-related differentially expressed genes (DEGs) in neuropathic pain. Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) network were used to analyze DEGs, respectively. Besides, the identified hub genes were submitted to the DGIdb database to find relevant therapeutic drugs. Results. A total of 91 neuroimmune-related DEGs were identified. The results of GO and pathway enrichment analyses were closely related to immune and inflammatory responses. PPI analysis showed two important modules and 8 hub genes: PTPRC, CD68, CTSS, RAC2, LAPTM5, FCGR3A, CD53, and HCK. The drug-hub gene interaction network was constructed by Cytoscape, and it included 24 candidate drugs and 3 hub genes. Conclusion. The present study helps us better understand the neuroimmune mechanism of neuropathic pain and provides some novel insights on NP treatment, such as modulation of microglia polarization and targeting bone resorption. Besides, CD68, CTSS, LAPTM5, FCGR3A, and CD53 may be used as early diagnostic biomarkers and the gene HCK can be a therapeutic target.

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RETRACTED: Analgesic effects of TLR4/NF-κB signaling pathway inhibition on chronic neuropathic pain in rats following chronic constriction injury of the sciatic nerve

Cited by 40 publications

References 35 publications

Link N suppresses interleukin-1β-induced biological effects on human osteoarthritic cartilage

Link N suppresses interleukin-1β-induced biological effects on human osteoarthritic cartilage

Analgesic effect of dexmedetomidine in rats after chronic constriction injury by mediating microRNA‐101 expression and the E2F2–TLR4–NF‐κB axis

Bioinformatic Analysis of Neuroimmune Mechanism of Neuropathic Pain

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