摘要
目的观察口颌面部炎性疼痛对大鼠中枢p38丝裂原激活蛋白激酶（p38 mitogen-activated protein kinase，p38MAPK）活性的影响。方法采用标准的福尔马林实验方法，在大鼠上唇皮下组织内注射2．5％福尔马林50ul建立福尔马林致口颌面部炎性疼痛模型，设正常对照组（对照组）、福尔马林组（FOR组）、福尔马林＋生理盐水组（FOR＋NS组）和福尔马林＋抑制剂阻断组（FOR＋SB组）。后两组大鼠小脑延髓池内置管，于造模前20min给予生理盐水或p38MAPK抑制剂（SB203580），观察动物行为变化。免疫荧光和蛋白质印迹法检测各组大鼠注射福尔马林20、60、120和180min时三叉神经脊束核尾侧亚核（Vc核）c—fos表达和p38MAPK、磷酸化p38MAPK（p-p38）含量的变化。结果各组Vc核总p38MAPK水平差异无统计学意义（P〉0．05），但FOR组和FOR＋NS组20min时p-p38水平[分别为（0．66±0．04）和（0．64±0．04）]比对照组（0．12±0．01）明显增加（P〈0．001）。各组p-p38在福尔马林注射后20min达高峰，之后逐渐下降。与FOR组和FOR＋NS组相比，FOR＋SB组大鼠由福尔马林引发的第Ⅱ期疼痛行为反应明显受到抑制（P〈0．05）；同时，Vc核的c-fos表达也减弱，在120min时减弱最明显（P〈0．01）。结论福尔马林致口颌面部炎性疼痛模型中p38MAPK活化水平增加，参与病理性疼痛的形成；p38MAPK抑制剂可明显缓解疼痛，进一步证实了p38MAPK在口颌面部炎性疼痛中的作用。
Objective To evaluate the potential role of p38 mitogen-activated protein kinase （MAPK） in the orofacial inflammatory pain. Methods SD rats received subcutaneous injection of 2. 5% formalin 50 ul in the left vibrissa pad to establish the inflammatory pain model. The rats were grouped into the control group, the formalin group （FOR group）, the formalin ＋ saline group （FOR ＋ NS group） and the formalin ＋ SB203580 group （ FOR ＋ SB group）. SB203580 or saline was inserted into the rat＇ s cisterna magna 20 minutes prior to the formalin injection, then the behavioral changes were tested. The immunofluorescence staining and Western blotting analysis were performed to examine e-los, p38MAPK and phosphorylated p38 （p-p38） activity in Vc at 20, 60, 120, 180 minutes after formalin injection. Results p38MAPK was constitutively expressed in Vc （ P 〉 0. 05 ） and p38MAPK was activated following formalin injection. Compared with the control group at 20 min （ 0. 12 ± 0. 01 ） , the level of p-p38 in FOR group （ 0. 66 ± 0. 04 ） and FOR ＋ NS group （ 0. 64 ± 0. 04 ） increased significantly （ P 〈 0. 001 ）. The expression of p-p38 peaked at 20 minutes, and then declined in each group. Intracisterna magna pretreatment of p38MAPK inhibitor SB203580 resulted in potent attenuation of phase II of pain behavior （ P 〈 0.05 ）, while the expression of c-fos was also inhibited, especially Activation of p38 mitogen-activated protein kinase at the point of 120 min （ P 〈 0. 01 ） . Conclusions played a major role in the development of orofacial inflammatory pain and it was verified by the experimental result that p38MAPK inhibitor SB203580 inhibited the formalin-induced orofaeial pain.
出处
《中华口腔医学杂志》
CAS
CSCD
北大核心
2012年第1期14-18,共5页
Chinese Journal of Stomatology
基金
基金项目：国家自然科学基金（30572066）
北京市自然科学基金（7082086）
