CB1 cannabinoid receptor agonist mouse VD-hemopressin(alpha) produced supraspinal analgesic activity in the preclinical models of pain.
CB1 cannabinoid receptor agonist mouse VD-hemopressin(alpha) produced supraspinal analgesic activity in the preclinical models of pain.
复制标题
CB1 大麻素受体激动剂小鼠 VD-加压素 (α) 在临床前疼痛模型中产生脊髓上镇痛活性。
DOI：
10.1016/j.brainres.2017.12.013
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发表时间：
2018
期刊：
影响因子：
2.9
通讯作者：
Fang Quan
中科院分区：
文献类型：
--
作者：
Zheng Ting;Zhang Run;Zhang Ting;Zhang Meng-Na;Xu Biao;Song Jing-Jing;Li Ning;Tang Hong-Hai;Wang Pei;Wang Rui;Fang Quan
小鼠vd -加压素（α） （VD-Hpα）是一种非肽，在体外功能试验中选择性地激活cb1大麻素受体，并在小鼠甩尾试验中发挥cb1介导的中枢抗感觉。本研究的目的是进一步研究椎上小鼠VD-Hpα在一系列临床前疼痛模型中的镇痛特性。我们的研究结果表明，经典大麻素激动剂WIN 55,212-2在临床前疼痛模型中产生脊柱上镇痛，这种镇痛被cb1拮抗剂/逆激动剂AM251选择性拮抗，而不被cb2拮抗剂AM630选择性拮抗。相比之下，在术后疼痛模型和福尔马林I期试验中，小鼠脑室内给药VD-Hpα可诱导小鼠剂量相关镇痛，cb1中性拮抗剂AM4113可显著降低小鼠镇痛，但AM251、AM630和阿片样物质和瞬时受体电位1型（TRPV1）受体的选择性拮抗剂则不能。此外，在醋酸诱导的内脏痛模型中，小鼠VD-Hpα在椎管上剂量依赖性地产生镇痛活性，其作用被AM4113和trpv1受体拮抗剂SB366791显著拮抗，而AM251、AM630和纳洛酮则不被拮抗。此外，小鼠中心注射VD-Hpα对福尔马林II期试验无显著影响。综上所述，目前的研究表明，cb1受体肽激动剂小鼠VD-Hpα通过一种新的cb1受体介导的机制，以一种与WIN 55,212-2可分离的药理学方式，在临床前疼痛模型中产生脊柱上镇痛。此外，trpv1受体也可能参与了小鼠vd - hpα诱导的内脏痛模型的镇痛。
Mouse VD-hemopressin(α) (VD-Hpα) is an undecapeptide that selectively activates CB1cannabinoid receptor inin vitrofunctional tests, and exerts CB1-mediated central antinociception in the mouse tail-flick assay. The aim of the present study was to further investigate the analgesic properties of supraspinal mouse VD-Hpα in a range of preclinical pain models. Our results indicated that the classical cannabinoid agonist WIN 55,212-2 produced supraspinal analgesia in preclinical pain models, which was selectively antagonized by the CB1antagonist/inverse agonist AM251, but not by the CB2antagonist AM630. In contrast, in post-operative pain model and phase I of formalin test, intracerebroventricular administration of mouse VD-Hpα induced dose-related analgesia in mice, which were markedly reduced by pretreatment with the CB1neutral antagonist AM4113, but not AM251, AM630 and the selective antagonists of opioid and Transient Receptor Potential Vanilloid Type 1 (TRPV1) receptors. Furthermore, in the acetic acid-induced visceral pain model, supraspinal administration of mouse VD-Hpα dose-dependently produced analgesic activities and the effects were significantly antagonized by both AM4113 and the TRPV1receptor antagonist SB366791, but not AM251, AM630 and naloxone. In addition, central injection of mouse VD-Hpα did not have significant effect in phase II of formalin test. Taken together, the present work suggests that the CB1receptor peptidic agonist mouse VD-Hpα produces supraspinal analgesia in preclinical pain models via a novel CB1receptor-mediated mechanism, in a manner pharmacologically dissociable from WIN 55,212-2. In addition, TRPV1receptor might also be involved in mouse VD-Hpα-induced analgesia in a visceral pain model.