CENTRAL GLIAL ACTIVATION MEDIATES CANCER-INDUCED PAIN IN A RAT FACIAL CANCER MODEL
CENTRAL GLIAL ACTIVATION MEDIATES CANCER-INDUCED PAIN IN A RAT FACIAL CANCER MODEL
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DOI：
10.1016/j.neuroscience.2011.02.007
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发表时间：
2011-04-28
期刊：
影响因子：
3.3
通讯作者：
Inenaga, K.
中科院分区：
文献类型：
--
作者：
Hidaka, K.;Ono, K.;Inenaga, K.
外周和中央胶质细胞的激活在炎症和神经损伤引起的疼痛超敏反应的发展中起重要作用。然而，神经胶质细胞在癌症疼痛中的参与还不清楚。本研究评价了外周和中央胶质细胞的活化和胶质细胞活化抑制剂丙戊茶碱对大鼠面部癌模型中疼痛相关行为的影响，该模型是步行者256 B细胞在单侧触须垫中生长直至接种后3-4天。与假手术组相比，接种组大鼠的面部梳理期延长，对辐射热刺激的退缩潜伏期缩短，对von Frey毛发刺激的退缩阈值降低，表明出现了自发性疼痛、热痛觉过敏和机械性异常性疼痛。在Iba 1和胶质细胞酸性蛋白（GFAP）的免疫染色中，虽然三叉神经节中的GFAP免疫阳性卫星胶质细胞没有形态学变化，但延髓背角中的Iba 1免疫阳性小胶质细胞和GFAP免疫阳性星形胶质细胞显示出细胞增殖的大胞体。从接种前开始每天腹膜内给予丙戊茶碱后，中枢神经胶质活化减弱，延长的面部梳理部分受到抑制，并且从第2天起诱导的异常性疼痛和痛觉过敏得到预防，而肿瘤大小没有变化。这些结果表明，在中枢神经系统中，而不是在周围神经系统中，神经胶质细胞的激活，介导的自发性疼痛的增强和异常性疼痛和痛觉过敏的发展在面部癌症模型的早期阶段。(c)2011年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Peripheral and central glial activation plays an important role in development of pain hypersensitivity induced by inflammation and nerve injury. However, the involvement of glial cells in cancer pain is not well understood. The present study evaluated the peripheral and central glial activation and the effect of an inhibitor of glial activation, propentofylline, on pain-related behaviors in a rat facial cancer model of the growth of Walker 256B cells in the unilateral vibrissal pad until days 3-4 post-inoculation. As compared with sham animals, the facial grooming period was prolonged, the withdrawal latency to radiant heat stimulation was shortened, and the withdrawal threshold by von Frey hair stimulation was decreased at the inoculated region, indicating the development of spontaneous pain, thermal hyperalgesia and mechanical allodynia. In immunostainings for Iba1 and glial fibrillary acidic protein (GFAP), although there were no morphological changes of GFAP-immunopositive satellite glial cells in the trigeminal ganglion, Iba1-immunopositive microglia and GFAP-immunopositive astrocytes in the medullary dorsal horn showed large somata with cell proliferation. After the daily i.p. administration of propentofylline beginning pre-inoculation, the central glial activation was attenuated, the prolonged facial grooming was partially suppressed, and the induced allodynia and hyperalgesia from day 2 were prevented, without a change in tumor size. These results suggest that glial activation in the CNS, but not in the peripheral nervous system, mediates the enhancement of spontaneous pain and the development of allodynia and hyperalgesia at an early stage in the facial cancer model. (c) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.