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Molecular Pain
Published in: Molecular Pain 1/2015

Open Access 01-12-2015 | Research

p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats

Authors: Masaaki Kiyomoto, Masamichi Shinoda, Kuniya Honda, Yuka Nakaya, Ko Dezawa, Ayano Katagiri, Satoshi Kamakura, Tomio Inoue, Koichi Iwata

Published in: Molecular Pain | Issue 1/2015

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Abstract

Background

Orofacial inflammatory pain is likely to accompany referred pain in uninflamed orofacial structures. The ectopic pain precludes precise diagnosis and makes treatment problematic, because the underlying mechanism is not well understood. Using the established ectopic orofacial pain model induced by complete Freund’s adjuvant (CFA) injection into trapezius muscle, we analyzed the possible role of p38 phosphorylation in activated microglia in ectopic orofacial pain.

Results

Mechanical allodynia in the lateral facial skin was induced following trapezius muscle inflammation, which accompanied microglial activation with p38 phosphorylation and hyperexcitability of wide dynamic range (WDR) neurons in the trigeminal spinal subnucleus caudalis (Vc). Intra-cisterna successive administration of a p38 mitogen-activated protein kinase selective inhibitor, SB203580, suppressed microglial activation and its phosphorylation of p38. Moreover, SB203580 administration completely suppressed mechanical allodynia in the lateral facial skin and enhanced WDR neuronal excitability in Vc. Microglial interleukin-1β over-expression in Vc was induced by trapezius muscle inflammation, which was significantly suppressed by SB203580 administration.

Conclusions

These findings indicate that microglia, activated via p38 phosphorylation, play a pivotal role in WDR neuronal hyperexcitability, which accounts for the mechanical hypersensitivity in the lateral facial skin associated with trapezius muscle inflammation.
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Metadata
Title
p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats
Authors
Masaaki Kiyomoto
Masamichi Shinoda
Kuniya Honda
Yuka Nakaya
Ko Dezawa
Ayano Katagiri
Satoshi Kamakura
Tomio Inoue
Koichi Iwata
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2015
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/s12990-015-0053-y

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