Senkyunolide I Relieves Neuropathic Pain Induced by Chronic Constriction Injury by Inhibiting Activation of Microglia

As an alternative to the use of narcotics, generally refractory to long-term effectiveness, for the management of neuropathic pain, we have explored the utility of senkyunolide I. Senkyunolide I is one of the bioactive components isolated from Ligusticum chuanxiong Hort known to exhibit multiple biological activities. In this study, we report senkyunolide I inhibition of chronic constriction injury induced neuropathic pain. Mechanistically, senkyunolide I inhibited chronic constriction injury induced apoptosis and the activity of microglia via extracellular signal regulated kinase pathway. We therefore suggest that senkyunolide I could serve as a promising drug for the treatment of neuropathic pain.

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Extracellular signal-regulated kinase activation in the chronic constriction injury model of neuropathic pain in anaesthetized rats

European Journal of Pain ◽

10.1002/j.1532-2149.2012.00181.x ◽

2012 ◽

Vol 17 (1) ◽

pp. 35-45 ◽

Cited By ~ 12

Author(s):

G.S. Borges ◽

E. Berrocoso ◽

A. Ortega-Alvaro ◽

J.A. Mico ◽

F.L. Neto

Keyword(s):

Neuropathic Pain ◽

Chronic Constriction Injury ◽

Kinase Activation ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Injury Model ◽

Anaesthetized Rats ◽

Chronic Constriction Injury Model

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Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Clinical Microbiology Reviews ◽

10.1128/cmr.00078-09 ◽

2010 ◽

Vol 23 (3) ◽

pp. 590-615 ◽

Cited By ~ 326

Author(s):

Soichiro Kanoh ◽

Bruce K. Rubin

Keyword(s):

Nuclear Factor Kappa B ◽

Biological Activities ◽

Mechanisms Of Action ◽

Nuclear Factor ◽

Diffuse Panbronchiolitis ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Regulation Of Cell Cycle ◽

Immunomodulatory Therapies

SUMMARY Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

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

January 2018 - Pain Physician ◽

10.36076/ppj.2015/18/e1073 ◽

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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