Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

Li, Donghua; Yan, Yurong; Lan, Yu; Duan, Yong

doi:10.4062/biomolther.2016.006

Cited by 22 publications

(21 citation statements)

References 28 publications

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“…The activated signaling pathway is accompanied by increased sensitivity to thermal and cold stimulations, indicating the aggravated pain behavior. These results support the fact that this cue is associated with neuropathic pain regulation (Li, Yan, Yu, & Duan, ). Therefore, the decreased content of IL‐6 by using MSCs could abate in turn the protein expressions of its downstream molecule p ‐JAK2 and consequently p ‐STAT3 (Al‐Massri et al, ).…”

Section: Mscs Therapy In Cipn and Peripheral Neuropathysupporting

confidence: 85%

Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

Al-Massri

Ahmed

El‐Abhar

2019

J Tissue Eng Regen Med

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Chemotherapeutic drugs may disrupt the nervous system and cause chemotherapyinduced peripheral neuropathy (CIPN) as side effects. There are no completely successful medications for the prevention or treatment of CIPN. Many drugs such as tricyclic antidepressants and anticonvulsants have been used for symptomatic treatment of CIPN. Unfortunately, these drugs often give only partial relief or have dose-limiting side effects. Thus, the treatment of CIPN becomes a challenge because of failure to regenerate and repair the injured neurons. Mesenchymal stem cell (MSC) therapy is a new attractive approach for CIPN. Evidence has demonstrated that MSCs play important roles in reducing oxidative stress, neuroinflammation, and apoptosis, as well as mediating axon regeneration after nerve damage in several experimental studies and some clinical trials. We will briefly review the pathogenesis of CIPN, traditional therapies used and their drawbacks as well as therapeutic effects of MSCs, their related mechanisms, future challenges for their clinical application, and the additional benefit of their combination with pharmacological agents. MSCs-based therapies may provide a new therapeutic strategy for patients suffering from CIPN where further investigations are required for studying their exact mechanisms. Combined therapy with pharmacological agents can provide another promising option for enhancing MSC therapy success while limiting its adverse effects.

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Section: Mscs Therapy In Cipn and Peripheral Neuropathysupporting

confidence: 85%

Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

Al-Massri

Ahmed

El‐Abhar

2019

J Tissue Eng Regen Med

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“…JAK2/STAT3 signal transduction is involved in the activation of glial cells and formation of neuropathic pain [ 13 ]. In the CCI model, the presence of neuropathic pain was accompanied by the high expression of JAK2 and STAT3, and the inhibition of the expression of these factors could significantly relieve pain [ 14 ]. Ion channel dysfunction is central to the pathogenesis of painful DNP.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy

et al. 2019

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Purpose The aim of the present study was to further elucidate the role of JAK2/STAT3-CAV-1-NR2B on painful diabetic neuropathy. Methods In vivo, the mechanical withdrawal threshold and thermal withdrawal latency were measured to evaluate neuropathic pain behaviors ( n = 8), while western blot ( n = 5) and an immunofluorescence double staining experiment ( n = 6) were performed to understand the molecular mechanism. In vitro, the individual culture of BV2 mouse microglia cell lines, the co-culture of BV2 mouse microglia cell lines and PC12 rat neuron cell lines, and western blot analysis were performed to understand the molecular mechanism between microglia and neurons. Results The expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B was upregulated in the dorsal horn of DNP rats throughout the experiment. Through the immunofluorescence double staining experiment, it was found that p-STAT3 was mainly expressed in activated microglia, and this condition can be stably maintained for approximately 2 weeks after the establishment of the DNP model. The intrathecal injection of JAK2 inhibitor AG490 can relieve the abnormal expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B, and relieve pain. The remission of AG490 began on the third day, and it could be stably sustained for 14 days. In vitro high-glucose induced the activation of p-STAT3 in microglia, thereby upregulating the expression of p-CAV-1 and p-NR2B in neurons in the co-culture system. JAK2 inhibitor AG490 can alleviate the abnormal expression of these proteins in the JAK2/STAT3-CAV-1-NR2B signaling pathway in vitro. Conclusions Microglial JAK2/STAT3 signaling probably contributes to neuropathic pain by activating the CAV-1-NR2B pathway.

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“…WP1066, as a STAT3 inhibitor can serve as a novel therapeutic agent in bCCI neuropathic pain rats (Xue et al, ). Down‐regulation of miR‐218 can relieve neuropathic pain by inhibiting STAT3 signaling activation in microglial cells (Li et al, ; Li & Zhao, ). In our study, we found that STAT3 was a target of miR‐544 and STAT3 over‐expression can lead to neuropathic pain development.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that microRNA‐93 is able to relieve neuropathic pain via inhibiting STAT3 (Yan et al, ). Procaine can suppress neuropathic pain in model rats through targeting JAK2/STAT3 (Li, Yan, Yu, & Duan, ).…”

Section: Introductionmentioning

confidence: 99%

XIST/miR‐544 axis induces neuropathic pain by activating STAT3 in a rat model

Jin¹,

Du²,

Zhao³

et al. 2018

Journal Cellular Physiology

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An increasing number of studies have reported that lncRNAs are responsible for the development of neuropathic pain. In our current study, chronic constriction injury (CCI) rat models were established and we observed that lncRNA XIST was greatly increased. Knockdown of XIST can relieve pain characteristics including both mechanical and thermal hyperalgesia in CCI rats. Meanwhile, XIST down-regulation could inhibit neuro-inflammation by reducing expression of inflammatory cytokines including tumor necrosis factor (TNF)-α, IL-1β, and IL-6 and in CCI rats. By performing bioinformatics technology, miR-544 was predicted to have interactions with XIST and dual-luciferase reporter assays validated the correlation between them. A negative correlation between miR-544 and XIST was observed by carrying out XIST loss or gain of function tests. miR-544 markedly alleviated neuropathic pain development in CCI rats via targeting inflammatory cytokines, which was reversed by XIST over-expression. Moreover, STAT3 was manifested to be a target gene of miR-544 by bioinformatics predictions and it was activated in CCI rats. Over-expression of STAT3 was able to induce neuropathic pain and miR-544 inhibited this process in vivo. Furthermore, XIST increased STAT3 expression by sponging miR-544 in neuropathic pain development. To conclude, our present study indicated that XIST can contribute to neuropathic pain progression in rats through down-regulating miR-544 and up-regulating STAT3. Our results suggested that XIST/miR-544/STAT3 axis can serve as a novel therapeutic target in neuropathic pain development.

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Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

Cited by 22 publications

References 28 publications

Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy

XIST/miR‐544 axis induces neuropathic pain by activating STAT3 in a rat model

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