Department of Anesthesiology, Nihon University School of Dentistry, Kandasurugadai, Chiyoda-ku, Tokyo, Japan.
PLoS One. 2012;7(8):e44055. doi: 10.1371/journal.pone.0044055. Epub 2012 Aug 24.
To evaluate the involvement of trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluR2 and GluR3 subunits in an acute inflammatory orofacial pain, we analyzed nocifensive behavior, phosphorylated extracellular signal-regulated kinase (pERK) and Fos expression in Vi/Vc, Vc and C1/C2 in GluR2 delta7 knock-in (KI), GluR3 delta7 KI mice and wild-type mice. We also studied Vc neuronal activity to address the hypothesis that trafficking of GluR2 and GluR3 subunits plays an important role in Vi/Vc, Vc and C1/C2 neuronal activity associated with orofacial inflammation in these mice. Late nocifensive behavior was significantly depressed in GluR2 delta7 KI and GluR3 delta7 KI mice. In addition, the number of pERK-immunoreactive (IR) cells was significantly decreased bilaterally in the Vi/Vc, Vc and C1/C2 in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice at 40 min after formalin injection, and was also significantly smaller in GluR3 delta7 KI compared to GluR2 delta7 KI mice. The number of Fos protein-IR cells in the ipsilateral Vi/Vc, Vc and C1/C2 was also significantly smaller in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice 40 min after formalin injection. Nociceptive neurons functionally identified as wide dynamic range neurons in the Vc, where pERK- and Fos protein-IR cell expression was prominent, showed significantly lower spontaneous activity in GluR2 delta7 KI and GluR3 delta7 KI mice than wild-type mice following formalin injection. These findings suggest that GluR2 and GluR3 trafficking is involved in the enhancement of Vi/Vc, Vc and C1/C2 nociceptive neuronal excitabilities at 16-60 min following formalin injection, resulting in orofacial inflammatory pain.
为了评估 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体 (AMPAR)GluR2 和 GluR3 亚基的贩运是否参与急性炎症性口腔面部疼痛，我们分析了伤害感受行为、磷酸化细胞外信号调节激酶 (pERK) 和 Fos 在 Vi/Vc、Vc 和 C1/C2 中的表达在 GluR2 delta7 敲入 (KI)、GluR3 delta7 KI 小鼠和野生型小鼠中的表达。我们还研究了 Vc 神经元的活动，以验证 GluR2 和 GluR3 亚基的贩运在这些小鼠与口腔炎症相关的 Vi/Vc、Vc 和 C1/C2 神经元活动中起着重要作用的假设。在 GluR2 delta7 KI 和 GluR3 delta7 KI 小鼠中，晚期伤害感受行为明显受到抑制。此外，与野生型小鼠相比，在福尔马林注射后 40 分钟，在 Vi/Vc、Vc 和 C1/C2 的双侧 GluR2 delta7 KI 和 GluR3 delta7 KI 小鼠中 pERK-免疫反应 (IR) 细胞的数量显著减少，并且在 GluR3 delta7 KI 小鼠中也明显小于 GluR2 delta7 KI 小鼠。福尔马林注射后 40 分钟，在同侧 Vi/Vc、Vc 和 C1/C2 中 Fos 蛋白-IR 细胞的数量在 GluR2 delta7 KI 和 GluR3 delta7 KI 小鼠中也明显少于野生型小鼠。在福尔马林注射后，在 Vc 中功能上被鉴定为宽动态范围神经元的伤害感受神经元中，pERK 和 Fos 蛋白-IR 细胞的表达明显更为明显，与野生型小鼠相比，GluR2 delta7 KI 和 GluR3 delta7 KI 小鼠中的自发活性明显降低。这些发现表明，GluR2 和 GluR3 的贩运参与了福尔马林注射后 16-60 分钟 Vi/Vc、Vc 和 C1/C2 伤害感受神经元兴奋性的增强，导致口腔炎症性疼痛。
