Department of Oral Diagnosis, Nihon University School of Dentistry, Tokyo 101-8310, Japan.
J Neurosci. 2013 May 1;33(18):7667-80. doi: 10.1523/JNEUROSCI.4968-12.2013.
Fractalkine (FKN) signaling is involved in mechanical allodynia in the facial skin following trapezius muscle inflammation. Complete Freund's adjuvant (CFA) injection into the trapezius muscle produced mechanical allodynia in the ipsilateral facial skin that was not associated with facial skin inflammation and resulted in FKN but not FKN receptor (CX3CR1) expression, and microglial activation was enhanced in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2). Intra-cisterna magna anti-CX3CR1 or anti-interleukin (IL)-1β neutralizing antibody administration decreased the enhanced excitability of Vc and C1-C2 neurons in CFA-injected rats, whereas intra-cisterna magna FKN administration induced microglial activation and mechanical allodynia in the facial skin. IL-1β expression and p38 mitogen-activated protein kinase phosphorylation were enhanced in activated microglia after CFA injection. The excitability of neurons whose receptive fields was located in the facial skin was significantly enhanced in CFA-injected rats, and the number of cells expressing phosphorylated extracellular signal-regulated kinase (pERK) following noxious mechanical stimulation of the facial skin was significantly increased in Vc and C1-C2. We also observed mechanical allodynia of the trapezius muscle as well as microglial activation and increased pERK expression in C2-C6 after noxious stimulation of the trapezius muscle in facial skin-inflamed rats. These findings suggest that FKN expression was enhanced in Vc and C1-C2 or C2-C6 following trapezius muscle or facial skin inflammation, microglia are activated via FKN signaling, IL-1β is released from the activated microglia, and the excitability of neurons in Vc and C1-C2 or C2-C6 is enhanced, resulting in the ectopic mechanical allodynia.
趋化因子（FKN）信号参与斜方肌炎症后面部皮肤的机械性痛觉过敏。将完全弗氏佐剂（CFA）注入斜方肌会导致同侧面部皮肤出现机械性痛觉过敏，但与面部皮肤炎症无关，并导致 FKN 而不是 FKN 受体（CX3CR1）表达增加，三叉神经脊束核尾侧亚核（Vc）和颈上脊髓（C1-C2）中的小胶质细胞激活增强。鞘内注射抗-CX3CR1 或抗白细胞介素（IL）-1β中和抗体可降低 CFA 注射大鼠 Vc 和 C1-C2 神经元的兴奋性增强，而鞘内注射 FKN 可诱导面部皮肤的小胶质细胞激活和机械性痛觉过敏。CFA 注射后，激活的小胶质细胞中 IL-1β 表达和 p38 丝裂原活化蛋白激酶磷酸化增强。其感受野位于面部皮肤的神经元的兴奋性明显增强，在 CFA 注射大鼠中，面部皮肤有害机械刺激后，表达磷酸化细胞外信号调节激酶（pERK）的细胞数量在 Vc 和 C1-C2 中显著增加。我们还观察到，在面部皮肤炎症大鼠的斜方肌受到有害刺激后，C2-C6 中斜方肌或面部皮肤炎症后 Vc 和 C1-C2 或 C2-C6 中的机械性痛觉过敏、小胶质细胞激活和 pERK 表达增加。这些发现表明，斜方肌或面部皮肤炎症后，FKN 在 Vc 和 C1-C2 或 C2-C6 中表达增强，小胶质细胞通过 FKN 信号激活，激活的小胶质细胞释放 IL-1β，Vc 和 C1-C2 或 C2-C6 中的神经元兴奋性增强，导致异位机械性痛觉过敏。
