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

Abstract

BACKGROUND:

The activation of mitogen-activated protein kinases (MAPKs) have been observed in synaptic plasticity processes of learning and memory in neuropathic pain. Cerebrospinal fluid-contacting 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 CSF-CN. 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.

• Authors: Chun-Guang Wang, Si-Yuan Song, Yan-Ling Ding, Shu-Qin Guo, Xin Liu, Shi Hao, Xin Li, Na Chen, Yu Zhang, Li-Cai Zhang
• Journal: Pain physician (Pain Physician) Vol. 18 Issue 6 Pg. E1073-81 (Nov 2015) ISSN: 2150-1149 [Electronic] United States
• PMID: 26606020 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic AMP Response Element-Binding Protein
• Mitogen-Activated Protein Kinase 7

Topics

• Animals
• Cyclic AMP Response Element-Binding Protein (cerebrospinal fluid)
• Enzyme Activation (physiology)
• Hyperalgesia (cerebrospinal fluid, enzymology)
• Male
• Mitogen-Activated Protein Kinase 7 (cerebrospinal fluid, metabolism)
• Neuralgia (cerebrospinal fluid, enzymology)
• Periaqueductal Gray (enzymology)
• Rats
• Rats, Sprague-Dawley