p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats.
p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats.
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DOI：
10.1186/s12990-015-0053-y
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发表时间：
2015-08-12
期刊：
影响因子：
3.3
通讯作者：
Iwata K
中科院分区：
文献类型：
--
作者：
Kiyomoto M;Shinoda M;Honda K;Nakaya Y;Dezawa K;Katagiri A;Kamakura S;Inoue T;Iwata K
口腔面部炎症性疼痛可能伴随着未发炎的口腔面部结构的牵涉性疼痛。异位疼痛排除了准确的诊断，并使治疗成为问题，因为潜在的机制尚未很好地了解。采用斜方肌注完全弗氏佐剂(CFA)诱导的异位口面部疼痛模型，分析激活的小胶质细胞p38磷酸化在异位口面部疼痛中的可能作用。斜方肌炎症可导致面部外侧皮肤机械性痛觉超敏，并伴有三叉神经脊束核尾侧亚核(Vc)大动态范围(WDR)神经元p38磷酸化和高兴奋性的小胶质细胞激活。脑池内连续给予p38丝裂原激活的蛋白激酶选择性抑制剂SB203580，可抑制小胶质细胞的激活及其p38的磷酸化。此外，SB203580可完全抑制面部外侧皮肤的机械性痛觉过敏，增强Vc内WDR神经元的兴奋性。斜方肌炎症可诱导Vc内小胶质细胞白介素1β的过度表达，SB203580可显著抑制斜方肌炎症反应。这些发现表明，通过p38磷酸化激活的小胶质细胞在WDR神经元的超兴奋性中起着关键作用，这是与斜方肌炎症相关的面部外侧皮肤机械超敏的原因。
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. 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. 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.