An anti-nociceptive role for ceftriaxone in chronic neuropathic pain in rats
An anti-nociceptive role for ceftriaxone in chronic neuropathic pain in rats
复制标题
头孢曲松对大鼠慢性神经病理性疼痛的抗伤害作用
DOI：
10.1016/j.pain.2009.11.014
复制
发表时间：
2010-02-01
期刊：
影响因子：
7.4
通讯作者：
Li, Li
中科院分区：
文献类型：
--
作者：
Hu, Yuyan;Li, Wenbin;Li, Li
胶质谷氨酸转运体-1(GLT-1)在维持谷氨酸稳态中起重要作用，并参与病理性疼痛的发生和维持。本研究旨在(1)观察头孢曲松(CEF)对坐骨神经慢性缩窄性神经损伤(CCI)所致慢性神经病理性疼痛模型的抗伤害性作用；(2)探讨脊髓GLT-1在此过程中的作用。CCI术后3d开始出现明显的热痛觉过敏和机械性超敏反应，持续至21d。免疫组织化学和Western印迹显示，这种长期的痛敏伴随着脊髓背角L4-L6节段GLT-1表达的显著下调。预防性和治疗性给予CEF分别有效地预防或逆转了脊髓背角热痛敏、机械性超敏和GLT-1下调的发展。为了进一步确定CEF的上述抗伤害性作用是否是上调脊髓GLT-1表达及其功能的结果，我们进一步观察了鞘内注射CEF的作用。结果表明，鞘内注射CEF可特异性上调脊髓背角GLT-1的表达和谷氨酸(H-3-Glu)的摄取，其抗伤害性作用与腹腔注射CEF相似。鞘内注射GLT-1反义寡核苷酸(AS-ODN)可显著抑制CEF的上述作用。这些结果表明，CEF通过上调脊髓GLT-1的表达及其功能而发挥抗伤害性作用。(C)2009年国际疼痛研究协会。爱思唯尔出版公司版权所有。
Glial glutamate transporter-1 (GLT-1) plays an essential role in the maintenance of glutamate homeostasis and is involved in the development and maintenance of pathological pain. The present study was undertaken (1) to observe the anti-nociceptive effects of ceftriaxone (Cef) in a chronic neuropathic pain model induced by chronic constrictive nerve injury (CCI) of the sciatic nerve and (2) to identify the role of spinal GLT-1 in the process. CCI induced significant thermal hyperalgesia and mechanical allodynia, which began from postoperative day 3 and lasted to day 21. This long-term hyperalgesia was accompanied by significant down-regulation of GLT-1 expression in the L4-L6 segments of the spinal dorsal horn, as revealed by immunohistochemistry and Western blot. Intraperitoneal preventive and therapeutic administration of Cef effectively prevented or reversed, respectively, the development of thermal hyperalgesia, mechanical allodynia, and GLT-1 down-regulation in the spinal dorsal horn. To further determine whether the above anti-nociceptive effects of Cef are a result of the up-regulation of spinal GLT-1 expression and its function, we further observed the effects of intrathecal administration of Cef in the same model. It was found that intrathecal administration of Cef led to the specific up-regulation of GLT-1 expression and glutamate uptake (H-3-glutamate) in the spinal dorsal horn, and similar anti-nociceptive effects to those of intraperitoneal administration of Cef. The above effects of intrathecal Cef administration were all significantly inhibited by intrathecal administration of GLT-1 antisense oligodeoxynucleotides (As-ODNs). These results indicate that Cef plays an anti-nociceptive role by up-regulating spinal GLT-1 expression and its function. (C) 2009 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.