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Published on: January 10, 2014
p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats
Masaaki Kiyomoto1, Masamichi Shinoda2, Kuniya Honda3
1Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. kiyomoto49@dent.showa-u.ac.jp.
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.
Insights
Inflammation in the trapezius muscle causes ectopic orofacial pain by activating microglia via p38 phosphorylation. Inhibiting this pathway reduces pain hypersensitivity and neuronal hyperexcitability.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Orofacial inflammatory pain can cause referred pain in uninflamed areas.
- The mechanisms behind ectopic orofacial pain are poorly understood, complicating diagnosis and treatment.
Purpose of the Study:
- To investigate the role of p38 phosphorylation in activated microglia in an established model of ectopic orofacial pain.
Main Methods:
- Induced ectopic orofacial pain using complete Freund's adjuvant (CFA) in the trapezius muscle.
- Administered a p38 mitogen-activated protein kinase inhibitor (SB203580) to assess its effects.
- Analyzed microglial activation, p38 phosphorylation, and neuronal excitability in the trigeminal spinal subnucleus caudalis (Vc).
Main Results:
- Trapezius muscle inflammation led to mechanical allodynia in facial skin, microglial activation with p38 phosphorylation, and Vc wide dynamic range (WDR) neuron hyperexcitability.
- SB203580 treatment suppressed microglial activation, p38 phosphorylation, facial allodynia, and Vc WDR neuron hyperexcitability.
- Muscle inflammation increased microglial interleukin-1β expression in Vc, which was reduced by SB203580.
Conclusions:
- Activated microglia, through p38 phosphorylation, are crucial for WDR neuron hyperexcitability.
- This microglial activation contributes to mechanical hypersensitivity in the face associated with trapezius muscle inflammation.
