Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu (700-412), Republic of Korea.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jan 10;36(1):52-9. doi: 10.1016/j.pnpbp.2011.10.007. Epub 2011 Oct 13.
The present study investigated the role of microglia and p38 MAPK in the development of mechanical allodynia in rats with compression of the trigeminal ganglion. Male Sprague-Dawley rats weighing 250-260 g were used. Under pentobarbital sodium anesthesia, the animals were mounted onto a stereotaxic frame and given injections of 4% agar solution (10 μL) to compress the trigeminal ganglion. The air-puff thresholds significantly decreased after compression of the trigeminal ganglion. On postoperative day 14, immunoreactivity to both OX-42 and p-p38 MAPK was up-regulated in the medullary dorsal horn as compared to the sham group. P-p38 MAPK was found to be co-localized with OX-42, but not with NeuN, a neuronal cell marker, or with GFAP, an astroglial cell marker. Intracisternal administration of 100 μg of minocycline significantly inhibited both mechanical allodynia and activation of microglia produced by compression of the trigeminal ganglion. Intracisternal administration of 0.1, 1, or 10 μg of SB203580, a p38 MAPK inhibitor, also significantly decreased mechanical allodynia and p38 MAPK activation in the trigeminal ganglion-compressed group. These results suggest that activation of p38 MAPK in the microglia is an important step in the development of mechanical allodynia in rats with compression of the trigeminal ganglion and that the targeted blockade of microglial p38 MAPK pathway is a potentially important new treatment strategy for trigeminal neuralgia-like nociception.
本研究探讨了小胶质细胞和 p38MAPK 在三叉神经节压迫大鼠机械性痛觉过敏发展中的作用。雄性 Sprague-Dawley 大鼠体重 250-260g。戊巴比妥钠麻醉下，将动物置于立体定向框架上，向三叉神经节注射 4%琼脂溶液（10μL）。三叉神经节压迫后，气吹阈值明显降低。术后第 14 天，与假手术组相比，牙髓背角中 OX-42 和 p-p38MAPK 的免疫反应性上调。发现 p-p38MAPK 与 OX-42 共定位，但与神经元细胞标志物 NeuN 或星形胶质细胞标志物 GFAP 不共定位。鞘内给予 100μg 米诺环素可显著抑制三叉神经节压迫引起的机械性痛觉过敏和小胶质细胞的激活。鞘内给予 0.1、1 或 10μg p38MAPK 抑制剂 SB203580 也显著降低了三叉神经节压迫组的机械性痛觉过敏和 p38MAPK 激活。这些结果表明，三叉神经节压迫大鼠机械性痛觉过敏发展中小胶质细胞中 p38MAPK 的激活是一个重要步骤，靶向阻断小胶质细胞 p38MAPK 通路可能是治疗三叉神经痛样痛觉过敏的一种潜在重要新策略。
