scholarly journals Quercetin Alleviates Neuropathic Pain in the Rat CCI Model by Mediating AMPK/MAPK Pathway

2021 ◽  
Vol Volume 14 ◽  
pp. 1289-1301
Author(s):  
Guangyao Ye ◽  
Chunyan Lin ◽  
Yu Zhang ◽  
Zihan Ma ◽  
Yuebo Chen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Mapk Pathway ◽  
Cci Model

scholarly journals Paeoniflorin and Albiflorin Attenuate Neuropathic Pain via MAPK Pathway in Chronic Constriction Injury Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Jianyu Zhou ◽  
Linyuan Wang ◽  
Jingxia Wang ◽  
Chun Wang ◽  
Zhihui Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Mapk Pathway ◽  
Biological Activities ◽  
Neuroprotective Effect ◽  
Interleukin 1 ◽  
Underlying Mechanism ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Necrosis Factor

Neuropathic pain remains as the most frequent cause of suffering and disability around the world. The isomers paeoniflorin (PF) and albiflorin (AF) are major constituents extracted from the roots ofPaeonia (P.) lactifloraPall. Neuroprotective effect of PF has been demonstrated in animal models of neuropathologies. However, only a few studies are related to the biological activities of AF and no report has been published on analgesic properties of AF about neuropathic pain to date. The aim of this study was to compare the effects of AF and PF against CCI-induced neuropathic pain in rat and explore the underlying mechanism. We had found that both PF and AF could inhibit the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway in spinal microglia and subsequent upregulated proinflammatory cytokines (interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α)). AF further displayed remarkable effects on inhibiting the activation of astrocytes, suppressing the overelevated expression of phosphorylation of c-Jun N-terminal kinases (p-JNK) in astrocytes, and decreasing the content of chemokine CXCL1 in the spinal cord. These results suggest that both PF and AF are potential therapeutic agents for neuropathic pain, which merit further investigation.

scholarly journals Persistent Rheb-induced mTORC1 activation in spinal cord neurons induces hypersensitivity in neuropathic pain

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Xiaqing Ma ◽  
Wenjie Du ◽  
Wenying Wang ◽  
Limin Luo ◽  
Min Huang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cell Cycle Progression ◽  
Mammalian Target Of Rapamycin ◽  
Firing Frequency ◽  
Small Gtpase ◽  
Hcn Channels ◽  
Spinal Cord Neurons ◽  
Mtorc1 Signaling ◽  
New Strategy ◽  
Cci Model

Abstract The small GTPase Ras homolog enriched in the brain (Rheb) can activate mammalian target of rapamycin (mTOR) and regulate the growth and cell cycle progression. We investigated the role of Rheb-mediated mTORC1 signaling in neuropathic pain. A chronic constriction injury (CCI) model was dopted. CCI induced obvious spinal Rheb expression and phosphorylation of mTOR, S6, and 4-E-BP1. Blocking mTORC1 signal with rapamycin alleviated the neuropathic pain and restored morphine efficacy in CCI model. Immunofluoresence showed a neuronal co-localization of CCI-induced Rheb and pS6. Rheb knockin mouse showed a similar behavioral phenotype as CCI. In spinal slice recording, CCI increased the firing frequency of neurons expressing HCN channels; inhibition of mTORC1 with rapamycin could reverse the increased spinal neuronal activity in neuropathic pain. Spinal Rheb is induced in neuropathic pain, which in turn active the mTORC1 signaling in CCI. Spinal Rheb-mTOR signal plays an important role in regulation of spinal sensitization in neuropathic pain, and targeting mTOR may give a new strategy for pain management.

Long non coding RNAs involved in MAPK pathway mechanism mediates diabetic neuropathic pain

2020 ◽  
Vol 44 (12) ◽  
pp. 2372-2379
Author(s):  
Xinlu Ren ◽  
Runan Yang ◽  
Lin Li ◽  
Xiumei Xu ◽  
Shangdong Liang
Keyword(s):  
Neuropathic Pain ◽  
Mapk Pathway ◽  
Diabetic Neuropathic Pain ◽  
Non Coding Rnas

scholarly journals Effect of TRPV4-p38 MAPK Pathway on Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Yu-Juan Qu ◽  
Xiao Zhang ◽  
Zhen-Zhen Fan ◽  
Juan Huai ◽  
Yong-Bo Teng ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Mapk Pathway ◽  
Intrathecal Injection ◽  
Ruthenium Red ◽  
Protein Expressions ◽  
Intermediary Role ◽  
Ectopic Discharges

The aim of this study was to investigate the relationships among TRPV4, p38, and neuropathic pain in a rat model of chronic compression of the dorsal root ganglion. Mechanical allodynia appeared after CCD surgery, enhanced via the intrathecal injection of 4α-phorbol 12,13-didecanoate (4α-PDD, an agonist of TRPV4) and anisomycin (an agonist of p38), but was suppressed by Ruthenium Red (RR, an inhibitor of TRPV4) and SB203580 (an inhibitor of p38). The protein expressions of p38 and P-p38 were upregulated by 4α-PDD and anisomycin injection but reduced by RR and SB203580. Moreover, TRPV4 was upregulated by 4α-PDD and SB203580 and downregulated by RR and anisomycin. In DRG tissues, the numbers of TRPV4- or p38-positive small neurons were significantly changed in CCD rats, increased by the agonists, and decreased by the inhibitors. The amplitudes of ectopic discharges were increased by 4α-PDD and anisomycin but decreased by RR and SB203580. Collectively, these results support the link between TRPV4 and p38 and their intermediary role for neuropathic pain in rats with chronic compression of the dorsal root ganglion.

scholarly journals The Up-regulation of TNF-α Maintains Trigeminal Neuralgia by Modulating MAPKs Phosphorylation and BKCa Channels in Trigeminal Nucleus Caudalis

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhan-ying Lu ◽  
Juan Fan ◽  
Li-hua Yu ◽  
Bei Ma ◽  
Li-ming Cheng
Keyword(s):  
Neuropathic Pain ◽  
Trigeminal Neuralgia ◽  
Mechanical Allodynia ◽  
Infraorbital Nerve ◽  
Therapeutic Effects ◽  
Trigeminal Nucleus ◽  
Trigeminal Nucleus Caudalis ◽  
Tnf Α ◽  
Brain Ventricle ◽  
Cci Model

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous available medical interventions, the therapeutic effects are not ideal. To control the pain attacks, the need for more contemporary drugs continues to be a real challenge. Our previous study reported that Ca2+-activated K+ channels (BKCa) channels modulated by mitogen-activated protein kinases (MAPKs) in the trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some research studies demonstrated that inflammatory cytokine tumor necrosis factor alpha (TNF-α) could promote neuropathic pain. Meanwhile, the trigeminal nucleus caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is responsible for processing sensory and pain signals from the peripheral orofacial area. Thus, this study is aimed to further investigate whether TNF-α and MAPKs phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BKCa channels. The results showed that TNF-α of the TNC region is upregulated significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) rats model, which displayed persistent facial mechanical allodynia. The normal rats with target injection of exogenous TNF-α to the fourth brain ventricle behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold decreased clearly. Meanwhile, the exogenous TNF-α increased the action potential frequency and reduced the BKCa currents of TNC neurons significantly, which could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI model rats, respectively. Taken together, our work suggests that the upregulation of TNF-α in the TNC region would cause the increase of MAPKs phosphorylation and then the negative regulation of BKCa channels, resulting in the TN.

scholarly journals Standard analgesics reverse burrowing deficits in a rat CCI model of neuropathic pain, but not in models of type 1 and type 2 diabetes-induced neuropathic pain

2018 ◽  
Vol 350 ◽  
pp. 129-138 ◽  
Author(s):  
Kris Rutten ◽  
Stacey A. Gould ◽  
Luke Bryden ◽  
Henri Doods ◽  
Thomas Christoph ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Neuropathic Pain ◽  
Cci Model

scholarly journals Microglia are Involved in Pruritus Induced by DNFB via the CX3CR1/p38 MAPK Pathway

2015 ◽  
Vol 35 (3) ◽  
pp. 1023-1033 ◽  
Author(s):  
Ying Zhang ◽  
Jia Yan ◽  
Rong Hu ◽  
Yu Sun ◽  
Yiwen Ma ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Intrathecal Administration ◽  
P38 Inhibitor ◽  
P38 Mapk Pathway ◽  
Chronic Itch ◽  
Repeated Applications ◽  
Chronic Pruritus

Background/Aims: Pruritus, also known as itch, is a common, unpleasant sensation that can be difficult to treat. Frequently, chronic itch is associated with the development of neuropathic pain resulting from nerve injury or insult. Previous studies have shown the involvement of spinal microglia in the development of neuropathic pain, but their role in chronic pruritus is unclear. Methods: For this study, we constructed a model of chronic pruritus in mice using repeated applications of 2, 4-dinitrofluorobenzene (DNFB) and showed prolonged scratching behavior in treated mice that continued for at least 7 d after the final DNFB treatment. Results: Scratching was accompanied by activation of spinal microglia and both were reduced by an inhibitor of microglial activity. We also showed that microglial activation entailed increased signaling in the p38 MAPK pathway, and treatment with a p38 inhibitor reduced scratching in DNFB-treated mice. We also examined the role of fractalkine/CX3CR1 signaling in the development of DNFB-induced pruritus and showed that intrathecal administration of antiserum against either CX3CR1or FKN inhibited p38 activity and decreased scratching. Conclusion: Our results suggest that microglia are involved in pruritus induced by DNFB via FKN/CX3CR1/p38MAPK pathways similar to those participating in the development of neuropathic pain.

scholarly journals Pirt Together with TRPV1 Is Involved in the Regulation of Neuropathic Pain

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Changming Wang ◽  
Leying Gu ◽  
Yonglan Ruan ◽  
Tana Gegen ◽  
Lei Yu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Transient Receptor Potential ◽  
Life Quality ◽  
Thermal Hyperalgesia ◽  
In Vitro Study ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Cci Model ◽  
Transient Receptor

Neuropathic pain is a chronic pain and reduces the life quality of patients substantially. Transient receptor potential vanilloid channel 1 (TRPV1), a nonselective cation channel, has been shown to play a crucial role in neuropathic pain. Although TRPV1 plays an important role in neuropathic pain, the mechanism of how TRPV1 was regulated in neuropathic pain remains unclear. Pirt is a membrane protein and binds to TRPV1 to enhance its activity. It was suggested that Pirt should also be involved in neuropathic pain. In this study, we investigated the role of Pirt in neuropathic pain (CCI model); the results show that mechanical allodynia and thermal hyperalgesia were alleviated in Pirt−/− mice in CCI models. TRPV1 expression was increased by immunofluorescence and real-time PCR experiments. The increase in TRPV1 expression was less in Pirt knockout mice in CCI models. Moreover, the number of capsaicin-responding neurons and the magnitude of evoked calcium response were attenuated in DRG neurons from Pirt−/− mice in CCI models. Finally, we found that the pain behavior attenuated in dysfunction of both Pirt and TRPV1 was much stronger than in dysfunction of Pirt or TRPV1 only in a CCI model in vitro study. Taken together, Pirt together with TRPV1 is involved in CCI-induced neuropathic pain.

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