大鼠三叉神经脊束核尾侧亚核内COX2过表达与牙正畸痛的相关性  

Correlation between the overexpression of COX2 in the trigeminal nucleus caudalis and orthodontic pain in rats

作　　者：牛乐 岳江涛 冯凯隆 梅江涛 贾晓康 戴先文 NIU Le;YUE Jiangtao;FENG Kailong;MEI Jiangtao;JIA Xiaokang;DAI Xianwen(Department of Orthopaedics, Xi’an Chang’an Hospital, Xi’an 710016, China)

机构地区：[1]西安市长安医院骨科,陕西西安710016

出　　处：《西部医学》2021年第8期1133-1137,1144,共6页Medical Journal of West China

基　　金：国家自然科学基金(81400991)。

摘　　要：目的探讨环氧合酶2(COX2)在实验性牙正畸痛(ETMP)大鼠三叉神经脊束核尾侧亚核(Vc)的表达变化以及与疼痛行为的相关性。方法24只SD大鼠分为正畸痛组(ETMP组)、假手术对照组(Sham组)和空白对照组(Naive组),每组8只。每组在造模前和造模后4 h、12 h、1 d、2 d、3 d、7 d先进行痛觉行为学检测,然后利用免疫组化染色、免疫荧光染色和Western blot检测Vc内COX2的表达变化,在痛觉阈值最低时间点延髓背侧脑室内注入各种环氧合酶抑制剂进行行为药理学检测,同时在延髓进行免疫荧光双重染色。结果与Sham组和Naive组比较,ETMP组在牙移动后4 h形成了显著的痛觉行为学表现,1 d达到巅峰(均P<0.05)。ETMP组Vc内COX2染色密度和表达量显著增加,COX2的表达增加与痛觉行为学呈现显著相关(均P<0.05)。ETMP组脑室内给予COX2特异抑制剂能够有效镇痛,而COX1或COX3的抑制剂无镇痛作用。免疫荧光双重染色显示,COX2由Vc内神经元生成,并且大部分COX2阳性神经元处于激活状态。结论Vc内COX2的上调参与了ETMP大鼠痛觉行为学的形成,在指导新型镇痛药物的研发和正畸痛的治疗方面,将具有积极的促进作用。Objective To observe the expression change of cyclooxygenase2(COX2)in the trigeminal nucleus caudalis(Vc)in a rat model of experimental tooth movement pain(ETMP)and to determine its correlation with pain behavioral performance.Methods Adult male Sprague-Dawley rats were divided into ETMP group,Sham group and Naive group.Elastic rubber band was inserted between the incisor and the first maxillary molar bilaterally to establish tooth movement model.The directed mouth wiping behavior was used to evaluate the pain during tooth movement.At different time points(0,4h,12h,1d,2d,3d and 7d after rubber band insertion),the immunostaining and Western blot of COX2 were performed in each group after the detection of pain behavior.The inhibitors of COX2,COX1 or COX3 was injected intracisternally in ETMP group at 1d after rubber band insertion.After injection,pain behavior was immediately measured.Meanwhile,double-labeling immunofluorescence of COX2 with NeuN or Fos was performed in Vc sections.Results Compared to Sham group and Naive group,the mouth wiping behaviour of ETMP group significantly increased at 4h after rubber band insertion,reached the highest value at 1 d(n=8/group;P<0.05).The immunostaining and expression of COX2 was significantly increased in Vc of ETMP group(P<0.05).The expression level of COX2 was found to be significantly correlated to the mouth wiping behaviour in ETMP group(P<0.001,r=0.868).Intracisternal treatment with NS-398(a selective COX2 inhibitor)exerted significant analgesic effect in ETMP group.However,intrathecal treatment with selective COX1 inhibitor and selective COX3 inhibitor had no effect on pain behavior.Double immunofluorescent staining showed all of the COX2-immunoreactive structures in Vc exhibited NeuN-immunopositive staining and most of these COX2-immunoreactive neurons were Fos-immunopositive.Conclusion The overexpression of COX2 contributes to tooth movement pain,and inhibiting Vc COX2 may represent a novel therapeutic strategy for clinical management of orthodontic pain.

关 键 词：环氧合酶 脊髓 三叉神经 疼痛 正畸 牙移动 

分 类 号：R781[医药卫生—口腔医学]