鞘内注射NOS抑制剂对神经痛大鼠脊髓背角内磷酸化CREB表达的影响

J4 ›› 2009, Vol. 35 ›› Issue (6): 1020-1023.

鞘内注射NOS抑制剂对神经痛大鼠脊髓背角内磷酸化CREB表达的影响

杨桐伟¹, 宋雪松¹, 王苹², 王春喜³

（1.吉林大学第一医院麻醉科|吉林长春 130021； 2. 吉林大学第一医院耳鼻咽喉-头颈外科研究所|吉林长春 130021；3. 吉林大学第一医院泌尿外科|吉林长春130021）

收稿日期:2009-05-20 出版日期:2009-11-28 发布日期:2009-11-28
通讯作者: 王春喜 E-mail:Tel:0431- 88782321,E-mail:chunxiwang@126.com
作者简介:杨桐伟（1966－）|男|吉林省九台市人|副教授|在读医学博士|主要从事临床麻醉与疼痛的基础研究。
基金资助:

吉林省科技厅科研基金资助课题（200505195）

Effects of intrathecal injection of NOS inhibitors on |phosphorylated CREB expression in spinal cord of CCD-induced neuropathic pain rats

YANG Dong-Wei¹, SONG Xue-Song¹, WANG Peng², WANG Chun-Xi³

(1.Department of Anesthesiology,First Hospital,Jilin University,Changchun 130021,China;2.Institute of Otorhinolaryngology and Head-Neck Surgery,First Hospital,Jilin University,Changchun 130021,China;3. Department of Urinary Surgery,First Hospital,Jilin University,Changchun 130021,China)

Received:2009-05-20 Online:2009-11-28 Published:2009-11-28

摘要/Abstract

摘要：

目的：观察鞘内注射一氧化氮合酶（NOS）抑制剂对神经病理性疼痛大鼠痛行为及脊髓背角内磷酸化cAMP反应元件结合蛋白（pCREB）表达的影响，阐明脊髓背角内不同信号传导通路在神经病理性疼痛中的交互作用。方法：成年雄性Wistar大鼠制备背根神经节压迫性损伤（CCD）模型,按照注射药物不同随机分为L-NAME组、AG组、8-Br-cGMP组、7-NI组、Cremophor组和PBS组，采用热痛刺激仪测定CCD大鼠鞘内注射前后热痛缩爪潜伏期的变化，应用免疫组织化学方法检测大鼠脊髓背角内pCREB的表达。结果：CCD第5天大鼠术侧脊髓背角内pCREB免疫反应阳性神经元明显增多，阳性神经元位于脊髓背角全层。与PBS组比较，L-NAME组、AG组和7-NI组于鞘内注射后2 h术侧脊髓背角内pCREB免疫反应阳性神经元数量明显减少（P<0.01），8-Br-cGMP组术侧脊髓背角内pCREB免疫反应阳性神经元数量增加（P<0.05），鞘内应用NOS抑制剂L-NAME、AG或7-NI组能够明显减少CCD大鼠脊髓背角中pCREB表达，
同时伴有大鼠痛行为的改善。结论：CREB参与介导NO-cGMP-PKG信号传导通路在CCD引起的神经病理性痛的形成与维持。

关键词: 一氧化氮；神经痛；脊髓；cAMP反应元件结合蛋白

Abstract:

To investigate the changes of phosphorylated CREB in spinal cord dorsal horn of rats underwent chronic compression of dorsal root ganglia (CCD) and effects of intrathecally administer NOS inhibitor L-NAME,AG or 7-NI and cGMP analogue 8-Br-cGMP on the expression of pCREB in dorsal horn and the changes in thermal hyperalgesia of rats.Methods 90 male adult Wistar rats were randomly divided into L-NAME,AG,8-Br-cGMP,7-NI,Cremophor and PBS groups.Different NOS inhibitors were injected intrathecally by microsyringe at the 5th day after CCD,the thermal paw withdrawal latencies were measured before injection and 0.5,2.0,6.0,12.0,24.0 h after treatment,the anti-nociceptive effects of agents were compared.The expression of pCREB was detected by immunohistochemical analysis 2 h after intrathecal injection.Results CCD significantly increased the expression of pCREB and pCREB positive neurons located in all laminae of bilateral spinal cord.The expression of pCREB in ispilateral and contralateral spinal cord showed no significant difference.Compared with PBS group,there was significant decreasing in number of pCREB positive neurons in L-NAME,AG and 7-NI groups(P<0.01），and there was markedly increasing in 8-Br-cGMP group（P<0.05）;Simultaneously,the intrathecal administer L-NAME,AG and 7-NI could significantly reverse thermal hyperalgesia induced by CCD
.Conclusion NO-cGMP-PKG signal pathway contribute to CCD-induced neuropathic pain.

Key words: nitric oxide；neuralgia；spinal;cAMP response-element binding protein

中图分类号:

R741.02

杨桐伟, 宋雪松, 王苹, 王春喜. 鞘内注射NOS抑制剂对神经痛大鼠脊髓背角内磷酸化CREB表达的影响[J]. J4, 2009, 35(6): 1020-1023.

YANG Dong-Wei, SONG Xue-Song, WANG Peng, WANG Chun-Xi. Effects of intrathecal injection of NOS inhibitors on |phosphorylated CREB expression in spinal cord of CCD-induced neuropathic pain rats[J]. J4, 2009, 35(6): 1020-1023.