...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >Attenuation of neuropathic pain by the nociceptin/orphanin FQ antagonist JTC-801 is mediated by inhibition of nitric oxide production.
【24h】

Attenuation of neuropathic pain by the nociceptin/orphanin FQ antagonist JTC-801 is mediated by inhibition of nitric oxide production.

机译：Nociceptin / orphanin FQ拮抗剂JTC-801对神经性疼痛的减轻是通过抑制一氧化氮的产生来介导的。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

At the spinal level, the involvement of nociceptin/orphanin FQ (N/OFQ) in pain transmission is controversial. JTC-801, a selective nonpeptidergic N/OFQ antagonist, is a good tool to examine the involvement of endogenous N/OFQ in pathophysiological conditions. In the present study, we studied the effect of JTC-801 on neuropathic pain induced by L5 spinal nerve transection in mice. Thermal hyperalgesia was evident on day 3 postsurgery and maintained during the 10-day experimental period. Oral administration of JTC-801 relieved the thermal hyperalgesia in neuropathic mice in a dose-dependent manner. Following L5 nerve transection, the increase in nitric oxide synthase (NOS) activity was observed in the superficial layer of dorsal horn and around the central canal in the spinal cord by NADPH diaphorase histochemistry. Using the novel fluorescent nitric oxide (NO) detection dye diaminofluorescein-FM, we confirmed that NO production increased in the spinal slice prepared from neuropathic mice and that the increase was more prominent in the ipsilateral side to the nerve transection than in the contralateral side. These increases in NOS activity and NO production in neuropathic mice were blocked by pretreatment of oral JTC-801. Although intraperitoneal injection of the nonselective NOS inhibitor NG.-nitro-L-arginine methyl ester transiently, but significantly, attenuated neuropathic hyperalgesia, inducible NOS-deficient mice showed neuropathic pain after L5 spinal nerve transection. These results suggest that N/OFQ is involved in the maintenance of neuropathic pain and that the analgesic effect of JTC-801 on neuropathic pain is mediated by inhibition of NO production by neuronal NOS.
机译：在脊柱水平上，痛觉敏/孤啡肽FQ（N / OFQ）是否参与疼痛传递尚存争议。 JTC-801是一种选择性的非肽能N / OFQ拮抗剂，是检查内源性N / OFQ在病理生理状况中的作用的良好工具。在本研究中，我们研究了JTC-801对L5脊髓神经横断所致小鼠神经性疼痛的作用。热痛觉过敏在术后3天很明显，并在10天的实验期内保持不变。口服JTC-801以剂量依赖性方式减轻了神经性小鼠的热痛觉过敏。 L5神经横断后，通过NADPH心肌黄递酶组织化学观察到，在背角表层和脊髓中央管周围，一氧化氮合酶（NOS）活性增加。使用新型的一氧化氮（NO）检测染料二氨基荧光素-FM，我们证实从神经性小鼠制备的脊髓切片中NO的产生增加，并且该增加在对侧神经切断的同侧比在对侧更明显。口服JTC-801的预处理可阻止神经病小鼠NOS活性的增加和NO的产生。虽然腹膜内注射非选择性NOS抑制剂NG.-硝基-L-精氨酸甲酯是短暂的，但明显减轻了神经性痛觉过敏，但可诱导的NOS缺陷小鼠在L5脊髓横断后表现出神经性疼痛。这些结果表明，N / OFQ参与了神经性疼痛的维持，并且JTC-801对神经性疼痛的镇痛作用是由神经元NOS抑制NO产生的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号