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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Potent spinal analgesia elicited through stimulation of NTS2 neurotensin receptors.
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Potent spinal analgesia elicited through stimulation of NTS2 neurotensin receptors.

机译：通过刺激NTS2神经降压素受体引起有效的脊髓镇痛作用。

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摘要

Intrathecal administration of the neuropeptide neurotensin (NT) was shown previously to exert antinociceptive effects in a variety of acute spinal pain paradigms including hotplate, tail-flick, and writhing tests. In the present study, we sought to determine whether some of these antinociceptive effects might be elicited via stimulation of low-affinity NTS2 receptors. We first established, using immunoblotting and immunohistochemical techniques, that NTS2 receptors were extensively associated with putative spinal nociceptive pathways, both at the level of the dorsal root ganglia and of the superficial layers of the dorsal horn of the spinal cord. We then examined the effects of intrathecal administration of NT or selective NTS2 agonists on acute thermal pain. Both NT and NTS2 agonists, levocabastine and Boc-Arg-Arg-Pro-Tyrpsi(CH2NH)Ile-Leu-OH (JMV-431), induced dose-dependent antinociceptive responses in the tail-flick test. The effects of levocabastine and of JMV-431 were unaffected by coadministration of the NTS1-specific antagonist 2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxy-phenyl)pyrazol-3-yl)carboxy lamino]tricyclo)3.3.1.1.(3.7))-decan-2-carboxylic acid (SR48692), confirming that they were NTS2 mediated. In contrast, the antinociceptive effects of NT were partly abolished by coadministration of SR48692, indicating that NTS1 and NTS2 receptors were both involved. These results suggest that NTS2 receptors play a role in the regulation of spinal nociceptive inputs and that selective NTS2 agonists may offer new avenues for the treatment of acute pain.
机译：鞘内注射神经肽神经降压素（NT）先前已显示出在各种急性脊柱疼痛范例中的镇痛作用，包括加热板，甩尾和扭体试验。在本研究中，我们试图确定是否可以通过刺激低亲和力NTS2受体来引发某些抗伤害感受的作用。我们首先使用免疫印迹和免疫组化技术建立了NTS2受体与假定的脊髓伤害性途径广泛相关的信息，包括脊髓背根神经节和脊髓背角浅层的水平。然后，我们检查了鞘内给予NT或选择性NTS2激动剂对急性热痛的影响。 NT和NTS2激动剂左卡泊汀和Boc-Arg-Arg-Pro-Tyrpsi（CH2NH）Ile-Leu-OH（JMV-431）在甩尾试验中均诱导了剂量依赖性抗伤害感受性反应。左旋卡巴汀和JMV-431的作用不受NTS1特异性拮抗剂2-[（1-（7-氯-4-喹啉基）-5-（2,6-二甲氧基-苯基）吡唑-3- yl）羧基lamino] tricyclo）3.3.1.1。（3.7））-癸-2-羧酸（SR48692），证实它们是NTS2介导的。相反，通过同时施用SR48692可以部分消除NT的抗伤害感受作用，表明NTS1和NTS2受体均参与其中。这些结果表明，NTS2受体在脊髓伤害性感受输入的调节中起作用，选择性的NTS2激动剂可能为急性疼痛的治疗提供新途径。

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