P38 Phosphorylation in Medullary Microglia Mediates Ectopic Orofacial Inflammatory Pain in Rats
Autor: | Masamichi Shinoda, Tomio Inoue, Ko Dezawa, Kuniya Honda, Koichi Iwata, Yuka Nakaya, Satoshi Kamakura, Masaaki Kiyomoto, Ayano Katagiri |
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Jazyk: | angličtina |
Předmět: |
Male
Orofacial pain Pathology medicine.medical_specialty Pyridines p38 mitogen-activated protein kinases Freund's Adjuvant Interleukin-1beta Models Neurological Inflammation p38 Mitogen-Activated Protein Kinases Injections Rats Sprague-Dawley Cellular and Molecular Neuroscience Facial Pain medicine Animals Phosphorylation Ectopic pain Skin Neurons Medulla Oblongata Referred pain Trigeminal spinal nucleus Microglia business.industry Research Imidazoles Interleukin-1β Enzyme Activation Trapezius muscle inflammation medicine.anatomical_structure Anesthesiology and Pain Medicine Freund's adjuvant Molecular Medicine medicine.symptom business Trapezius muscle |
Zdroj: | Molecular Pain |
ISSN: | 1744-8069 |
DOI: | 10.1186/s12990-015-0053-y |
Popis: | 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. |
Databáze: | OpenAIRE |
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