Activation of glia and microglial p38 MAPK in medullary dorsal horn contributes to tactile hypersensitivity following trigeminal sensory nerve injury
Activation of glia and microglial p38 MAPK in medullary dorsal horn contributes to tactile hypersensitivity following trigeminal sensory nerve injury
复制标题
DOI：
10.1016/j.pain.2005.12.023
复制
发表时间：
2006-04-01
期刊：
影响因子：
7.4
通讯作者：
Oh, SB
中科院分区：
文献类型：
--
作者：
Piao, ZG;Cho, IH;Oh, SB
已知神经胶质激活有助于脊髓感觉神经损伤后的疼痛超敏反应。在这项研究中，我们研究了下牙槽神经和颏神经横断（IAMNT）后，髓背角（MDH）中胶质细胞活化导致触觉超敏反应的机制。在2小时，1，3，7，14，28和60天，分别使用OX-42和GFAP抗体的免疫组织化学分析监测小胶质细胞和星形胶质细胞的活化。触觉敏感性在IAMNT后1天显著增加，并持续28天。小胶质细胞的活化，主要观察到在MDH的浅层，开始在第1天，最大的在第3天，并维持到14天后IAMNT。星形胶质细胞的激活延迟相比，小胶质细胞，更深刻的在7和14天比3天后IAMNT。IAMNT后60 d，触觉敏感性和胶质细胞活性均逐渐降低，并恢复到基础水平。IAMNT后28 d，三叉神经节神经元无明显丢失，提示初级传入神经中枢终末的退行性改变可能与胶质细胞活性无关。米诺环素，小胶质细胞活化的抑制剂，减少小胶质细胞的活化，抑制p38丝裂原活化蛋白激酶（MAPK）在小胶质细胞的活化，并显着减弱疼痛超敏反应的发展，在这个模型中。这些结果表明，MDH中胶质细胞的活化在神经病理性疼痛的发生发展中起重要作用，而过度活化的小胶质细胞中p38 MAPK的活化在IAMNT模型中参与了疼痛超敏反应。(c)2006年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Glial activation is known to contribute to pain hypersensitivity following spinal sensory nerve injury. In this study, we investigated mechanisms by which glial cell activation in medullary dorsal horn (MDH) would contribute to tactile hypersensitivity following inferior alveolar nerve and mental nerve transection (IAMNT). Activation of microglia and astrocytes was monitored at 2 h, 1, 3, 7, 14, 28, and 60 days using immunohistochemical analysis with OX-42 and GFAP antibodies, respectively. Tactile hypersensitivity was significantly increased at 1 day, and this lasted for 28 days after IAMNT. Microglial activation, primarily observed in the superficial laminae of MDH, was initiated at 1 day, maximal at 3 days, and maintained until 14 days after IAMNT. Astrocytic activation was delayed compared to that of microglia, being more profound at 7 and 14 days than at 3 days after IAMNT. Both tactile hypersensitivity and glial activation appeared to gradually reduce and then return to the basal level by 60 days after IAMNT, There was no significant loss of trigeminal ganglion neurons by 28 days following IAMNT, suggesting that degenerative changes in central terminals of primary afferents might not contribute to glial activation. Minocycline, an inhibitor of microglial activation, reduced microglial activation, inhibited p38 mitogen-activated protein kinase (MAPK) activation in microglia, and significantly attenuated the development of pain hypersensitivity in this model. These results suggest that glial activation in MDH plays an important role in the development of neuropathic pain and activation of p38 MAPK in hyperactive microglia contributes to pain hypersensitivity in IAMNT model. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.