Lidocaine suppresses the increased extracellular signal-regulated kinase/cyclic AMP response element-binding protein pathway and pro-inflammatory cytokines in a neuropathic pain model of rats

2011 ◽  
Vol 28 (2) ◽  
pp. 106-111 ◽  
Author(s):  
Jin D Joo ◽  
Jin W Choi ◽  
Jang H In ◽  
Hong S Jung ◽  
Jung A Lee ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cyclic Amp ◽  
Inflammatory Cytokines ◽  
Pain Model ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Element Binding Protein ◽  
Neuropathic Pain Model ◽  
Cyclic Amp Response Element ◽  
Pro Inflammatory Cytokines

Pro-inflammatory cytokines involvement in the hesperidin antihyperalgesic effects at peripheral and central levels in a neuropathic pain model

2017 ◽  
Vol 25 (2) ◽  
pp. 265-269 ◽  
Author(s):  
A. I. Carballo-Villalobos ◽  
M. E. González-Trujano ◽  
N. Alvarado-Vázquez ◽  
F. J. López-Muñoz
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Cytokines ◽  
Pain Model ◽  
Neuropathic Pain Model ◽  
Pro Inflammatory Cytokines

scholarly journals Anti-proliferative effect of pro-inflammatory cytokines in cultured β cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: protective role of glucagon-like peptide -1

2008 ◽  
Vol 41 (1) ◽  
pp. 35-44 ◽  
Author(s):  
M Blandino-Rosano ◽  
G Perez-Arana ◽  
J M Mellado-Gil ◽  
C Segundo ◽  
M Aguilar-Diosdado
Keyword(s):  
Inflammatory Cytokines ◽  
Protective Role ◽  
Β Cells ◽  
Β Cell ◽  
Extracellular Signal Regulated Kinase ◽  
Proliferative Effect ◽  
Extracellular Signal ◽  
Glucagon Like Peptide ◽  
Pro Inflammatory Cytokines

Pancreatic β-cell homeostasis is a balance between programmed cell death (apoptosis) and regeneration. Although autoimmune diabetes mellitus type 1 (DM1) is the most-studied cause of β-cell mass loss by pro-inflammatory cytokine-induced apoptosis, influences of a pro-inflammatory environment on β-cell regenerative response have been poorly studied. In this study, we assess the anti-proliferative effect of pro-inflammatory cytokines and glucose concentration on rat pancreatic β cells and the potential protective role of glucagon-like peptide (GLP-1). Apoptotic and proliferating islet cells were stained using the DeadEnd Fluorimetric TUNEL System and 5-bromo-2′-deoxyuridine label respectively, in the presence–absence of varying concentrations of glucose, pro-inflammatory cytokines, and GLP-1. The potential signaling pathways involved were evaluated by western blot. Considerable anti-proliferative effects of pro-inflammatory cytokines interleukin (IL)-1β, interferon (IFN)-γ, and tumour necrosis factor-α (TNF-α) were observed. The effects were synergistic and independent of glucose concentration, and appeared to be mediated by the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activation, the signaling pathway involved in β-cell replication. GLP-1 completely reversed the cytokine-induced inhibition of ERK phosphorylation and increased β-cell proliferation threefold in cytokine-treated cultures. While pro-inflammatory cytokines reduced islet cell ERK1/2 activation and β-cell proliferation in pancreatic islet culture, GLP-1 was capable of reversing this effect. These data suggest a possible pharmacological application of GLP-1 in the treatment of early stage DM1, to prevent the loss of pancreatic β cells as well as to delay the development of overt diabetes.

Inhibition of the Extracellular Signal-regulated Kinase Pathway Restores the Discogenic Phenotype of Inflammatory Intervertebral Disc Cells

2021 ◽  
Author(s):  
Adel Tekari ◽  
Alessandro Marazza ◽  
Benjamin Gantenbein
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Inflammatory Cytokines ◽  
Gelatin Zymography ◽  
Erk Pathway ◽  
Nucleus Pulposus Cells ◽  
Necrosis Factor Alpha ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Pro Inflammatory Cytokines

Abstract Background: Intervertebral disc (IVD) degeneration is a spinal disease caused by trauma and/or repetitive mechanical overloading of the spine which triggers inflammatory response pathways. Long-term disc inflammation may lead to development of spinal pseudoarthrosis. The aim of the present study was to elucidate the role of the extracellular signal-regulated kinase (ERK) pathway in inflammation-induced IVD cells. Methods: Inflammatory human nucleus pulposus cells (NPC) were stimulated using tumor necrosis factor alpha (TNFα) and the ERK pathway was blocked using a selective molecule-based inhibitor U0126. Gene expression of catabolic and anabolic events, pro-inflammatory, and NPC markers were investigated. The enzymatic activity of matrix metalloproteinases (MMP)2/9 were determined by gelatin zymography. The cytoxicity of U0126 concentrations on NPC was quantified using resazurin assay, and the specificity of U0126 on ERK1/2 signaling was determined.Results: The pro-inflammatory cytokines like MMP3/13 and interleukin 6 in nucleus pulposus (NP) inflammatory conditions were down-regulated by U0126 and a trend towards an increase of the NP-specific collagen type 2, aggrecan and keratin 19 was observed suggesting a recovery of the NP phenotype. U0126 does not seem to have effect on prostaglandin production, aggrecanases and some anabolic genes. We confirmed that U0126 selectively blocks the ERK phosphorylation and U0126 affects the cells metabolic activity only for high concentrations. Conclusions: Inhibition of ERK signaling down-regulates important metalloproteinase, pro-inflammatory cytokines, and up-regulates NP markers in order to restore the discogenic phenotype of inflammatory NPC.

scholarly journals Extracellular Signal-Regulated Kinase 5 in the Cerebrospinal Fluid-Contacting Nucleus Contributes to Neuropathic Pain in Rats

2015 ◽  
Vol 6;18 (6;11) ◽  
pp. E1073-E1082
Author(s):  
Li-Cai Zhang
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Element Binding Protein ◽  
Thermal Hypersensitivity

Background: The activation of mitogen-activated protein kinases (MAPKs) have been observed in synaptic plasticity processes of learning and memory in neuropathic pain. Cerebrospinal fluidcontacting nucleus (CSF-CN) has been identified with the onset and persistence of neuropathic pain. However, whether extracellular signal-regulated protein kinase 5 (ERK5), a member of MAPKs, in CSF-CN participates in neuropathic pain has not been studied yet. Objective: The aim of the present study was to identify the role of ERK5 in CSF-CN on the formation and development of neuropathic pain, and to investigate its possible mechanism. Study Design: Controlled animal study. Setting: University laboratory. Methods: After a chronic constriction injury (CCI) model was produced, BIX02188 was dissolved in 1% DMSO and injected into the lateral ventricles LV in a volume of 3 μl with different doses (0.1 μg, 1 μg, 10 μg). Mechanical allodynia and thermal hypersensitivity behavioral test, immunofluorescence, and western blot technique were used in this research. Result: Following CCI, mechanical allodynia and thermal hypersensitivity were developed within a day, peaked at 14 days, and persisted for 21 days. ERK5 was remarkably activated by CCI in CSFCN. Moreover, selective inhibiting of p-ERK5 expression in CSF-CN by BIX02188 could significantly relieve CCI-induced mechanical allodynia and thermal hypersensitivity, accompanying with the decreased phosphorylation of cAMP response-element binding protein (CREB) in CSF-CN. Limitations: More underlying mechanism(s) of the role of ERK5 in CSF-CN on the formation and development of neuropathic pain will be needed to explore in future research. Conclusion: These findings suggest activation of ERK5 in CSF-CN might contribute to the onset and development of neuropathic pain and its role might be partly accomplished by p-CREB. Key words: Neuropathic pain, extracellular signal-regulated kinase 5, distal cerebrospinal fluidcontacting neurons, cerebrospinal fluid-contacting nucleus, chronic constriction injury, cAMP response-element binding protein

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