<scp>COX</scp>‐2 is required for the modulation of spinal nociceptive information related to ephrinB/EphB signalling

Zhou, Xi‐Lang; Wang, Y.; Zhang, C.-J.; Lu, Yu; Cao, Jun‐Li; Yan, Min

doi:10.1002/ejp.657

Cited by 13 publications

(6 citation statements)

References 53 publications

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“…Intrathecally injected ephrinB activates their EphB receptors and produces long-lasting MWT and TWL ( 23 , 24 ). However, which subtype mainly mediating nociceptive pain remains to be elucidated.…”

Section: Resultsmentioning

confidence: 99%

EphrinB/EphB signaling contributes to spinal nociceptive processing via calpain‑1 and caspase‑3

et al. 2018

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Previous studies have indicated that an important subfamily of receptor tyrosine kinases, ephrins and their receptors, are important in pain signaling, particularly in spinal nociceptive processing. In the present study, the role of the ephrin/Eph signaling pathway was confirmed, and it was shown that this signaling was also involved in spinal nociceptive processing through the actions of calpain-1 and caspase-3. First, the ephrinB ligands, ephrinB1-Fc or ephrinB2-Fc, were introduced into experimental mice via intrathecal injection, and it was found that this injection induced marked time- and dose-dependent mechanical allodynia and thermal hyperalgesia, accompanied by increased levels of calpain-1 and caspase-3 in the spinal cord. MDL28170, an inhibitor of calpain-1, reversed the behavioral effects and ameliorated the increases in calpain-1 and caspase-3. Second, it was found that the administration of EphB1 between L5 and L6 in mice inhibited the mechanical allodynia and thermal hyperalgesia induced by chronic constrictive injury. In addition, to demonstrate the cell phenotypes responsible for the increased levels of calpain-1 and caspase-3 in the spinal cord following injection with ephrinB2-Fc, double immunofluorescent labeling was performed, which indicated that calpain-1 and caspase-3 were localized in neurons, but not in astrocytes or microglial cells. In conclusion, the present study suggested that ephrinB/EphB signaling contributes to spinal nociceptive processing via the actions of calpain-1 and caspase-3.

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Section: Resultsmentioning

confidence: 99%

EphrinB/EphB signaling contributes to spinal nociceptive processing via calpain‑1 and caspase‑3

et al. 2018

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“…In a previous study, the treatment that inhibited this interleukin was shown to attenuate allodynia and hyperalgesia [36]. However, it induces a variety of diseases through overproduction [37].…”

Section: Inflammatory Cytokines Levels In the Supernatant Of The Raw ...mentioning

confidence: 96%

“…Compared to the control induced with LPS only, significant reductions in IL-1β, IL-6, and IL-12 expressions were found in the cells treated with quercetin and WOEE (Figure 5a-c) in a dose-dependent manner. In a previous study, it was reported that quercetin inhibited the secretion of LPS-activated IL-1β, IL-6, and TNF-α proteins in the culture medium [37]. Inflammatory cytokines are a type of glycoprotein released from cells that are used for signaling for immune responses.…”

Section: Inflammatory Cytokines Levels In the Supernatant Of The Raw ...mentioning

confidence: 99%

Antioxidant and Anti-Inflammatory Effects of Ethanol Extract from Whole Onion (Allium cepa L.) with Leaves

Kim

et al. 2022

Agriculture

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This study was conducted to evaluate and to increase the usage of the whole onion (Allium cepa L.), which is composed of a small bulb and many leaves that are discarded as by-products before the bulbs grow. Whole onions are harvested early in immature condition, which allows the other onion bulbs to grow well. We compared its functional activities with those of quercetin, which is one of its major components. The antioxidant activities of ethanol extract from the whole onion (WOEE) were measured by DPPH and ABTS radical scavenging activities, and superoxide dismutase (SOD) and catalase (CAT) activities. The anti-inflammatory effects of WOEE were investigated in RAW 264.7 macrophages treated with LPS by analyzing cytokine levels and expressions using ELISA kits and RT-PCR assays, respectively. WOEE showed high antioxidant effects on DPPH and ABTS radical scavenging activities, and SOD and CAT activities. WOEE significantly reduced the production of nitric oxide, IL-1β, IL-6, and TNF-α, and/or their mRNA expressions in a dose-dependent manner. The results indicated that whole onions had antioxidant and anti-inflammatory effects, which were comparable with quercetin and may be used as a novel potential therapeutic candidate.

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“…Given the important roles of eph-rinB-EphB signaling in the generation and maintenance of chronic pain, researchers have always focused on exploring the upstream and downstream signal pathway (11,12) have demonstrated that some MAPKs such as ERK1/2, p38, and JNK, are involved in the ephrinB-EphB signaling-induced hyperalgesia. Our previous studies have consecutively proved that phosphatidy linositol 3-kinase (PI3K), protein kinase A (PKA), and protein kinase Cγ (PKCγ) act as the downstream factors of ephrinB-EphB signaling in modulating the spinal nociceptive information (7,(43)(44)(45). In the present study, we hypothesized that ERK5/CREB pathway may act as the downstream signal pathway of ephrinB-EphB signaling in modulating pain transduction.…”

Section: Discussionmentioning

confidence: 80%

EphrinB-EphB Signaling Induces Hyperalgesia through ERK5/CREB Pathway in Rats

Sun

Wang

et al. 2017

Pain Phys

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Background: There are numerous studies implicating that EphB receptors and ephrinB ligands play important roles in modulating the transduction of spinal nociceptive information. EphrinB-EphB signaling may contribute to hyperalgesia via various kinds of downstream molecules, the mechanisms of which have not been completely understood. Objective: The aim of the present study was to identify whether ephrinB-EphB signaling could contribute to hyperalgesia through ERK5/CREB pathway. Study Design: Controlled animal study. Setting: University laboratory. Methods: This study attempted to detect the changes of pain behaviors and the protein level of p-ERK5 and p-CREB by activating EphB receptors in the spinal cord of rats. To further confirm our hypothesis, we designed LV-siRNA for knockdown of spinal ERK5. When ERK5 was inhibited, we recorded the changes of spinal p-CREB expression and the pain behaviors of rats after activating EphB receptors. We also confirmed this conclusion in rat CCI model. Statistical analyses were performed using GraphPad Prism 5. Results: Intrathecal injection of ephrinB2-Fc in rats evoked thermal hyperalgesia and mechanical allodynia, along with activation of ERK5 and CREB in the spinal cord. Knockdown of ERK5 inhibited ephrinB2-Fc-induced CREB activation and hyperalgesia. Blocking EphB receptors prevented CCI-induced neuropathic pain and spinal ERK5/CREB activation. Limitations: More underlying mechanisms that underlie the relationship between ephrinBEphB signaling and ERK5/CREB pathway will need to be explored in future studies. Conclusions: Our study suggests that ERK5/CREB pathway plays important roles in the transduction of nociceptive information associated with ephrinB-EphB signaling. This study provides further understanding of the downstream mechanisms of ephrinB-EphB signaling and helps to explore new targets for treating pathological pain. Key words: EphrinB-EphB signaling, MAPK, ERK5, CREB, hyperalgesia, pain, CCI, NMDA

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COX‐2 is required for the modulation of spinal nociceptive information related to ephrinB/EphB signalling

Abstract: These results confirmed the important involvement of COX-2 in the modulation of spinal nociceptive information related to ephrinBs-EphBs signalling.

Cited by 13 publications

References 53 publications

EphrinB/EphB signaling contributes to spinal nociceptive processing via calpain‑1 and caspase‑3

EphrinB/EphB signaling contributes to spinal nociceptive processing via calpain‑1 and caspase‑3

Antioxidant and Anti-Inflammatory Effects of Ethanol Extract from Whole Onion (Allium cepa L.) with Leaves

EphrinB-EphB Signaling Induces Hyperalgesia through ERK5/CREB Pathway in Rats

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