Effects of neuropeptide FF system on CB1 and CB2 receptors mediated antinociception in mice
Effects of neuropeptide FF system on CB1 and CB2 receptors mediated antinociception in mice
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神经肽FF系统对CB1和CB2受体介导的小鼠镇痛作用的影响
DOI：
10.1016/j.neuropharm.2011.09.013
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发表时间：
2012-02-01
影响因子：
4.7
通讯作者：
Wang, Rui
中科院分区：
文献类型：
--
作者：
Fang, Quan;Han, Zheng-Lan;Wang, Rui
已经证明，阿片和大麻素受体系统可以产生类似的信号转导和行为效应。神经肽FF（NPFF）属于阿片调节肽家族。据报道，NPFF通过与阿片系统的相互作用在疼痛和镇痛控制中发挥重要作用。我们感兴趣的是，是否中枢和外周大麻素的抗伤害性感受可以通过脊髓上NPFF系统的影响。本研究考察了NPFF和相关肽对非选择性大麻素受体激动剂WIN 55，212-2通过脊髓上和足底内途径诱导的抗伤害活性的影响。在小鼠中，WIN 55，212-2的中枢和外周抗伤害感受分别由大麻素CB 1和CB 2受体介导。有趣的是，NPFF的中枢给药以剂量依赖性方式显著降低大麻素的中枢和外周镇痛。相反，dNPA和NPVF（i. c. v.），NPFF 2和NPFF 1受体的两种高度选择性激动剂，剂量依赖性地增强了由脑室内和足底内注射WIN 55，212-2引起的抗伤害感受。此外，用NPFF受体选择性拮抗剂RF 9（i. c. v.）在伤害感受性测定中显著降低NPFF和相关肽的大麻素调节活性。这些数据为NPFF和大麻素系统之间的功能性相互作用提供了第一个证据，表明中枢NPFF受体的激活干扰大麻素介导的中枢和外周抗伤害感受。有趣的是，目前的工作可能铺平了道路，一个新的战略，使用大麻素和NPFF激动剂联合治疗疼痛management.This文章的一部分，题为“创伤后应激障碍”的特刊。(C)2011爱思唯尔有限公司版权所有。
It has been demonstrated that opioid and cannabinoid receptor systems can produce similar signal transduction and behavioural effects. Neuropeptide FF (NPFF) belongs to an opioid-modulating peptide family. NPFF has been reported to play important roles in control of pain and analgesia through interactions with the opioid system. We were interested in whether the central and peripheral antinociception of cannabinoids could be influenced by supraspinal NPFF system. The present study examined the effects of NPFF and related peptides on the antinociceptive activities induced by the non-selective cannabinoid receptors agonist WIN55,212-2, given by supraspinal and intraplantar routes. In mice, the central and peripheral antinociception of WIN55,212-2 are mediated by cannabinoid CB1 and CB2 receptors, respectively. Interestingly, central administration of NPFF significantly reduced central and peripheral analgesia of cannabinoids in dose-dependent manners. In contrast, dNPA and NPVF (i.c.v.), two highly selective agonists for NPFF2 and NPFF1 receptors, dose-dependently augmented the antinociception caused by intracerebroventricular and intraplantar injection of WIN55,212-2. Additionally, pretreatment with the NPFF receptors selective antagonist RF9 (i.c.v.) markedly reduced the cannabinoid-modulating activities of NPFF and related peptides in nociceptive assays. These data provide the first evidence for a functional interaction between NPFF and cannabinoid systems, indicating that activation of central NPFF receptors interferes with cannabinoid-mediated central and peripheral antinociception. Intriguingly, the present work may pave the way for a new strategy of using combination treatment of cannabinoid and NPFF agonists for pain management.This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. (C) 2011 Elsevier Ltd. All rights reserved.