Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi'an Jiaotong University College of Stomatology, Xi'an, Shaanxi, China.
Department of Medical Imaging, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Neurogastroenterol Motil. 2018 Feb;30(2). doi: 10.1111/nmo.13161. Epub 2017 Jul 21.
We previously developed an animal model to examine mechanisms that underlie the emergence of visceral hypersensitivity modeling pain characteristics of temporomandibular disorder (TMD) patients with comorbid irritable bowel syndrome (IBS). In ovariectomized (OVx) rats with estradiol (E2) replacement, visceral hypersensitivity developed subsequent to masseter muscle inflammation followed by repeated forced swim (FS) stress. The purpose of this study was to investigate whether activation of extracellular signal-regulated kinase (ERK) in the spinal cord contributes to visceral hypersensitivity in this overlapping pain model.
In OVx with E2 replacement rats masseter muscle inflammation was followed by 3 day FS (comorbid condition). Depression-like behaviors were assessed by sucrose preference and in the elevated plus maze, and visceral sensitivity was measured by the visceromotor response (VMR) to colorectal distention. The protein level of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in the L6-S2 dorsal spinal cord was analyzed by western blot.
FS stress decreased sucrose consumption in E2 replaced rats in sucrose preference test. The expression of p-ERK1/2 in the L6-S2 dorsal spinal cord increased significantly in E2 with comorbid rats. Intrathecal injection of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor PD98059 blocked the visceral hypersensitivity induced by masseter muscle inflammation combined with FS stress.
CONCLUSIONS & INFERENCES: These data indicate that ERK1/2 activation contributes to the visceral hypersensitivity evoked by craniofacial inflammation pain combined with stress. The results may provide a new therapeutic avenue for alleviating overlapping pain conditions.
我们之前开发了一种动物模型来研究潜在机制，这些机制是颞下颌关节紊乱症（TMD）伴发肠易激综合征（IBS）患者内脏敏感性出现的基础。在雌激素（E2）替代的卵巢切除（OVx）大鼠中，咀嚼肌炎症后紧接着进行反复强迫游泳（FS）应激，会出现内脏敏感性。本研究旨在探讨脊髓细胞外信号调节激酶（ERK）的激活是否有助于这种重叠性疼痛模型中的内脏敏感性。
在 E2 替代的 OVx 大鼠中，咀嚼肌炎症后进行 3 天 FS（合并条件）。通过蔗糖偏好和高架十字迷宫评估抑郁样行为，通过结直肠扩张的内脏运动反应（VMR）测量内脏敏感性。通过 Western blot 分析 L6-S2 背根脊髓中 ERK1/2 和磷酸化 ERK1/2（p-ERK1/2）的蛋白水平。
FS 应激降低了 E2 替代大鼠在蔗糖偏好测试中的蔗糖消耗。E2 合并大鼠 L6-S2 背根脊髓中 p-ERK1/2 的表达显著增加。鞘内注射丝裂原活化蛋白激酶（MAPK）激酶（MEK）抑制剂 PD98059 可阻断咀嚼肌炎症合并 FS 应激引起的内脏敏感性。
这些数据表明 ERK1/2 的激活有助于咀嚼肌炎症疼痛与应激共同引起的内脏敏感性。这些结果可能为缓解重叠性疼痛提供一种新的治疗途径。
