Peripheral anti-nociceptive effect of nociceptin/orphanin FQ in inflammation and stress-induced colonic hyperalgesia in rats
Peripheral anti-nociceptive effect of nociceptin/orphanin FQ in inflammation and stress-induced colonic hyperalgesia in rats
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DOI：
10.1016/j.pain.2008.12.007
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发表时间：
2009-02-01
期刊：
影响因子：
7.4
通讯作者：
Bueno, Lionel
中科院分区：
文献类型：
--
作者：
Agostini, Simona;Eutamene, Helene;Bueno, Lionel
孤啡肽/孤啡肽（N/OFQ）及其NOP受体存在于中枢神经系统和外周，在胃肠道功能和疼痛的调节中起重要作用。本研究的目的是研究中枢和外周N/OFQ-NOP受体系统在基础条件下以及在炎症和应激触发的两种肠道超敏反应模型中对结直肠扩张（CRD）的伤害性反应中的作用。在基础和炎症后条件下测试雄性Wistar大鼠，即，在IC TNBS滴注（80 mg/Kg）后5天，并接受N/OFQ（2 nmol/Kg IP）、UFP-101（选择性NOP受体拮抗剂，10 nmol/Kg IP）、N/OFQ+UFP-101、N/OFQ（0.5 nmol/大鼠ICV）或媒介物。雌性大鼠在基础和部分束缚应激后接受相同的药理学处理。使用恒压器进行CRD，并通过肌电图记录腹部收缩。在基础条件下，注射N/OFQ、ICV和IP并没有改变基础内脏敏感性。在TNBS和应激诱发的痛觉过敏中，IP而不是ICV注射N/OFQ显著减少腹部收缩次数。外周注射UFP-101可拮抗N/OFQ效应。此外，在炎症后结肠炎中，与媒介物相比，单独注射的UFP-101加剧了对CRD的内脏痛觉过敏。这些发现表明，在大鼠中，N/OFQ，仅外周注射，减少由炎症或应激引发的内脏高敏感性，而不影响基础敏感性。N/OFQ内脏抗痛觉过敏作用涉及外周NOP受体。在炎症后而非急性应激性结肠炎模型中，N/OFQ能系统被内源性激活。(C)2008年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Nociceptin/orphanin FQ (N/OFQ) and its NOP receptors are present in the central nervous system and in the periphery playing important roles in the modulation of gastrointestinal functions and pain. The aim of this study was to investigate the role of central and peripheral N/OFQ-NOP receptor system in the nociceptive response to colorectal distension (CRD) in basal condition and in two models of gut hypersensitivity triggered by both inflammation and stress. Male Wistar rats were tested in basal and in post-inflammatory conditions, i.e., 5 days after IC TNBS instillation (80 mg/Kg) and received N/OFQ (2 nmol/Kg IP), UFP-101 (a selective NOP receptor antagonist, 10 nmol/Kg IP), N/OFQ+UFP-101, N/OFQ (0.5 nmol/rat ICV) or vehicle. Female rats were tested in basal and after partial restraint stress receiving the same pharmacological treatment. CRD was performed using barostat and abdominal contractions were recorded by electromyography. In basal condition, N/OFQ, ICV and IP injected, did not modify basal visceral sensitivity. Both in TNBS arid stress-induced hyperalgesia, IP but not ICV injection of N/OFQ significantly decreased the number of abdominal contractions. Peripheral injection of UFP-101 antagonized N/OFQ effect. Moreover, in post-inflammatory colitis, UFP-101, injected alone, exacerbated visceral hyperalgesia to CRD compared with vehicle. These findings indicate that in rats, N/OFQ, only peripherally injected, reduces visceral hypersensitivity triggered by inflammation or stress Without affecting basal sensitivity. N/OFQ visceral anti-hyperalgesic effect involves peripheral NOP receptors. In a post-inflammatory, but not in an acute stress colitis model, N/OFQergic system is endogenously activated. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.