Agostini Simona, Eutamene Helene, Broccardo Maria, Improta Giovanna, Petrella Carla, Theodorou Vassillia, Bueno Lionel
INRA, EI-Purpan, UMR 1054 Neuro-Gastroenterology and Nutrition Unit, 180 Chemin de Tournefeuille - BP3, 31931 Toulouse Cedex 9, Toulouse, France Department of Human Physiology and Pharmacology, University La Sapienza, Rome, Italy.
Pain. 2009 Feb;141(3):292-299. doi: 10.1016/j.pain.2008.12.007. Epub 2009 Jan 14.
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 and 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.
痛敏肽/孤啡肽FQ（N/OFQ）及其NOP受体存在于中枢神经系统和外周，在调节胃肠功能和疼痛方面发挥着重要作用。本研究的目的是探讨中枢和外周N/OFQ-NOP受体系统在基础状态以及由炎症和应激引发的两种肠道超敏反应模型中对结直肠扩张（CRD）伤害性反应的作用。雄性Wistar大鼠在基础状态和炎症后条件下接受测试，即在腹腔注射三硝基苯磺酸（TNBS，80mg/kg）5天后，并接受N/OFQ（2nmol/kg腹腔注射）、UFP-101（一种选择性NOP受体拮抗剂，10nmol/kg腹腔注射）、N/OFQ+UFP-101、N/OFQ（0.5nmol/大鼠脑室内注射）或溶剂。雌性大鼠在基础状态和部分束缚应激后接受相同的药物治疗。使用压力调节器进行CRD，并通过肌电图记录腹部收缩情况。在基础状态下，脑室内和腹腔注射N/OFQ均未改变基础内脏敏感性。在TNBS和应激诱导的痛觉过敏中，腹腔注射而非脑室内注射N/OFQ显著减少了腹部收缩次数。外周注射UFP-101拮抗了N/OFQ的作用。此外，在炎症后结肠炎中，单独注射UFP-101与溶剂相比，加剧了对CRD的内脏痛觉过敏。这些发现表明，在大鼠中，仅外周注射的N/OFQ可降低由炎症或应激引发的内脏超敏反应，而不影响基础敏感性。N/OFQ的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。
