Robust spinal neuroinflammation mediates mechanical allodynia in Walker 256 induced bone cancer rats.
Robust spinal neuroinflammation mediates mechanical allodynia in Walker 256 induced bone cancer rats.
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强烈的脊髓神经炎症介导 Walker 256 诱导的骨癌大鼠的机械异常性疼痛
DOI：
10.1186/1756-6606-5-16
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发表时间：
2012-05-20
期刊：
影响因子：
3.6
通讯作者：
Wang YQ
中科院分区：
文献类型：
--
作者：
Mao-Ying QL;Wang XW;Yang CJ;Li X;Mi WL;Wu GC;Wang YQ
已有研究表明，与神经性疼痛和炎症性疼痛不同，癌性疼痛（cancer induced pain，CIP）中存在星形胶质细胞和/或小胶质细胞的显著和持续激活。本研究采用改良的大鼠骨癌模型，探讨脊髓Toll样受体4（TLR 4）诱导的胶质神经炎症在癌性疼痛中的作用。CIP大鼠模型包括单侧胫骨内注射步行者256乳腺癌。接种步行者256后9天，观察到双侧脊髓背角中星形胶质细胞和小胶质细胞的强烈活化以及显著的双侧机械性异常性疼痛。这种神经炎症的特征是胶质细胞酸性蛋白（GFAP，星形胶质细胞标志物）和OX-42（小胶质细胞标志物）的免疫染色增强，以及IL-1β、IL-6和TNF-α mRNA水平升高。I.T.在接种步行者256后第12天，给予氟柠檬酸盐（神经胶质代谢抑制剂，1 nmol）或米诺环素（小神经胶质抑制剂，100 μg）具有显著的抗异常性疼痛作用。纳洛酮（一种非立体选择性TLR 4信号传导阻滞剂，60 μg，i.t.）还显著减轻机械性异常性疼痛，同时阻断炎性细胞因子mRNA的增加。结果表明，脊髓TLR 4可能在持续的胶质细胞活化中发挥重要作用，胶质细胞活化是CIP中强烈和持续的脊髓神经炎症的关键因素。这一结果可能有助于临床医生和研究人员更好地了解复杂癌痛的机制。
It has been reported that remarkable and sustained activation of astrocytes and/or microglia occurs in cancer induced pain (CIP), which is different from neuropathic and inflammatory pain. The present study was designed to investigate the role of spinal Toll-like receptor 4 (TLR4) induced glial neuroinflammation in cancer induced pain using a modified rat model of bone cancer. The rat model of CIP consisted of unilateral intra-tibial injection with Walker 256 mammary gland carcinoma. Nine days after Walker 256 inoculation, a robust activation of both astrocytes and microglia in bilateral spinal dorsal horn was observed together with significant bilateral mechanical allodynia. This neuroinflammation was characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker), and an elevated level of IL-1β, IL-6 and TNF-α mRNA. I.t. administration of fluorocitrate (an inhibitor of glial metabolism, 1 nmol) or minocycline (an inhibitor of microglia, 100 μg) has significant anti-allodynic effects on day 12 after Walker 256 inoculation. Naloxone (a nonstereoselective TLR4 signaling blocker, 60 μg, i.t.) also significantly alleviated mechanical allodynia and simultaneously blocked the increased inflammatory cytokine mRNA. The results suggested that spinal TLR4 might play an important role in the sustained glial activation that critically contributed to the robust and sustained spinal neuroinflammation in CIP. This result could potentially help clinicians and researchers to better understand the mechanism of complicated cancer pain.
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影响因子：
8.8
作者：
Ito, Naomi;Obata, Hideaki;Saito, Shigeru
通讯作者：
Saito, Shigeru
影响因子：
15.1
作者：
Hutchinson, Mark R.;Zhang, Yingning;Shridhar, Mitesh;Evans, John H.;Buchanan, Madison M.;Zhao, Tina X.;Slivka, Peter F.;Coats, Benjamen D.;Rezvani, Niloofar;Wieseler, Julie;Hughes, Travis S.;Landgraf, Kyle E.;Chan, Stefanie;Fong, Stephanie;Phipps, Simon;Falke, Joseph J.;Leinwand, Leslie A.;Maier, Steven F.;Yin, Hang;Rice, Kenner C.;Watkins, Linda R.
通讯作者：
Watkins, Linda R.
影响因子：
6.2
作者：
Bettoni, Isabella;Comelli, Francesca;Costa, Barbara
通讯作者：
Costa, Barbara
DOI：
10.1084/jem.192.4.595
发表时间：
2000-08-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Häcker H;Vabulas RM;Takeuchi O;Hoshino K;Akira S;Wagner H
通讯作者：
Wagner H
影响因子：
7.4
作者：
Ledeboer, A;Sloane, EM;Watkins, LR
通讯作者：
Watkins, LR