Wang Cunjin, Song Siyuan, Zhang Yang, Ge Yali, Fang Xiangzhi, Huang Tianfeng, Du Jin, Gao Ju
Clinical Medical College of Yangzhou University &Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Yangzhou, China.
Jiangsu Key Laboratory of Anesthesiology &Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou, China.
Sci Rep. 2015 Sep 29;5:14553. doi: 10.1038/srep14553.
Administration of lipopolysaccharide (LPS) by various routes produces profound inflammatory pain hypersensitivity. However, the molecular events that induce this response remain largely uncharacterized. In the present study, we sought to elucidate the role of the Rho/Rho kinase (ROCK) pathway in the release of tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) following injection of LPS into the mouse paw, which is associated with nociceptive behavior. The spinal cord of LPS-treated mice showed increased active GTP-bound RhoA and upregulation of ROCK2 and c-fos compared to the normal saline group. Furthermore, the inflammation-related cytokines TNF-α and IL-1β were markedly increased in the spinal dorsal horn after intraplantar injection of LPS. However, the latter effects were prevented by prophylactic intrathecal administration of the Rho inhibitor (C3 exoenzyme) or the ROCK inhibitor (Y27632). Collectively, our results suggest that the Rho/ROCK signaling pathway plays a critical role in LPS-induced inflammatory pain and that this pathway is coincident with the release of the pro-nociceptive cytokines TNF-α and IL-1β, which produces hyperalgesia.
通过各种途径给予脂多糖（LPS）会产生严重的炎性疼痛超敏反应。然而，诱导这种反应的分子事件在很大程度上仍未明确。在本研究中，我们试图阐明Rho/Rho激酶（ROCK）通路在向小鼠爪注射LPS后肿瘤坏死因子-α（TNF-α）和白细胞介素1β（IL-1β）释放中的作用，这与伤害感受行为有关。与生理盐水组相比，LPS处理小鼠的脊髓显示活性GTP结合的RhoA增加，ROCK2和c-fos上调。此外，足底注射LPS后，脊髓背角中炎症相关细胞因子TNF-α和IL-1β明显增加。然而，鞘内预防性给予Rho抑制剂（C3外切酶）或ROCK抑制剂（Y27632）可预防后一种效应。总体而言，我们的结果表明，Rho/ROCK信号通路在LPS诱导的炎性疼痛中起关键作用，并且该通路与促伤害感受细胞因子TNF-α和IL-1β的释放一致，后者会产生痛觉过敏。
