Department of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Neurosci Lett. 2014 Jan 24;559:88-93. doi: 10.1016/j.neulet.2013.11.049. Epub 2013 Dec 4.
Previous studies have shown that spinal Homer 1b/c plays an important role in the maintenance of chronic inflammatory pain induced by complete Freund's adjuvant (CFA). This study investigated the possible mechanism underlying Homer 1b/c mediating CFA-induced inflammatory pain. Chronic inflammation was induced by CFA injection into the left hind ankle of the rat. Homer 1b/c antisense or missense oligonucleotides were administered intrathecally (10μg/10μl) from 5 to 8 days following the onset of inflammation. Immunohistochemistry was conducted to detect the expression of phosphorylated cAMP response element binding protein (pCREB) and Fos protein in the spinal dorsal horn. Intrathecal administration of Homer 1b/c antisense oligonucleotides not only markedly reduced the expression of Homer 1b/c protein, but also attenuated CFA-induced inflammation, spinal CREB phosphorylation, and Fos expression. These results demonstrate for the first time that Homer 1b/c regulates CREB phosphorylation and c-fos activation in the spinal dorsal horn during the maintenance of chronic inflammatory pain, suggesting that Homer 1b/c may be involved in the development of CFA-induced inflammation.
先前的研究表明，脊髓 Homer 1b/c 在完全弗氏佐剂（CFA）诱导的慢性炎症性疼痛的维持中起着重要作用。本研究旨在探讨 Homer 1b/c 介导 CFA 诱导的炎症性疼痛的可能机制。通过向大鼠左后踝内注射 CFA 诱导慢性炎症。在炎症开始后的第 5 至 8 天，通过鞘内给药（10μg/10μl）给予 Homer 1b/c 反义或错义寡核苷酸。免疫组织化学用于检测脊髓背角中磷酸化 cAMP 反应元件结合蛋白（pCREB）和 Fos 蛋白的表达。Homer 1b/c 反义寡核苷酸鞘内给药不仅显著降低了 Homer 1b/c 蛋白的表达，而且减轻了 CFA 诱导的炎症、脊髓 CREB 磷酸化和 Fos 表达。这些结果首次表明，在慢性炎症性疼痛的维持过程中，Homer 1b/c 调节脊髓背角中 CREB 磷酸化和 c-fos 激活，表明 Homer 1b/c 可能参与 CFA 诱导的炎症的发展。
