Nociceptin and the ORL-1 ligand [Phe1ψ (CH2-NH)Gly2]nociceptin(1-13)NH2 exert anti-opioid effects in the Freund's adjuvant-induced arthritic rat model of chronic pain
Nociceptin and the ORL-1 ligand [Phe1ψ (CH2-NH)Gly2]nociceptin(1-13)NH2 exert anti-opioid effects in the Freund's adjuvant-induced arthritic rat model of chronic pain
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DOI：
10.1038/sj.bjp.0702884
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发表时间：
1999-11-01
影响因子：
7.3
通讯作者：
Ongini, E
中科院分区：
文献类型：
--
作者：
Bertorelli, R;Corradini, L;Ongini, E
1伤害素(NC)刺激阿片受体样1(ORL-1)受体产生痛觉过敏，并逆转阿片类药物的抗伤害效应。大多数关于NC中枢效应的研究都是使用急性疼痛模型进行的。NC在慢性炎症中的作用尚不清楚。2本研究旨在评估NC在弗氏佐剂诱导的单关节炎大鼠模型中的作用。评估了在该模型中作为镇痛剂的药物的效果。NC、NCNH2的影响。ORL-1配体[Phe(1)Psi(CH2-NH)Gly(2)]NC(1-13)NH2([FIG]NC(1-13)NH，)也被单独或与吗啡联合研究。NCNH2(10nmol，i.c.v.)表现出痛觉过敏效应(赋形剂治疗组S为-4.5±-0.9 vs-0.7+-0.8)。[F/G]NC(1-13)NH2(0.01-10nmol，i.c.V.)佐剂组动物的痛敏反应(-3.3+/-0.6 vs-0.3+/-0.5 S；10nmoL)。和[F/G]NC(1-13)NH2(0.01-1nmol，i.c.v)，吗啡(3 mg kg(-1)，S.C.)后30min。在佐剂性关节炎大鼠模型中，NC和[F/G]NC(1-13)NH2均具有抗阿片肽的作用。5在佐剂性关节炎大鼠模型中，NC和[F/G]NC(1-13)NH2均具有抗阿片肽的作用。此外，NCNH2和[F/G]NC(1-13)NH2单独给药时可引起痛觉过敏。进一步的研究和确定中枢作用的ORL-1拮抗剂对于更好地理解NC在疼痛机制中的作用是必要的。
1 Stimulation of the opioid receptor-like1 (ORL-1) receptor by nociceptin (NC) produces hyperalgesia and reverses the antinociceptive effects induced by opioids. Most studies concerning the central effects of NC were conducted using acute pain models. The role NC may play in chronic inflammation remains unelucidated.2 The present study was undertaken to assess the action of NC in the Freund's adjuvant-induced monoarthritic rat model. The effects of drugs known to act as analgesics in this model were evaluated. The effects of NC, NCNH2. and the ORL-1 ligand, [Phe(1)Psi(CH2-NH)Gly(2)]NC(1-13)NH2 ([FIG]NC(1-13)NH,), were also studied alone or in association with morphine.3 NC (1-30 nmol, i.c.v.) was inactive, whilst NCNH2 (10 nmol, i.c.v.) exerted hyperalgesic effects (-4.5+/-0.9 vs -0.7+/-0.8 s of vehicle-treated animals). [F/G]NC(1-13)NH2 (0.01-10 nmol, i.c.v.) induced hyperalgesia in the arthritic paw (--3.3 +/- 0.6 vs --0.3 +/- 0.5 s of vehicle-treated animals; 10 nmol).4 Both NC (0.01-10 nmol, i.c.v.) and [F/G]NC(1-13)NH2 (0.01-1 nmol, i.c.v), 30 min after morphine (3 mg kg(-1), s.c. induced an immediate and short-lived reversal of morphine effects (2.6 +/- 0.3 vs 10.4 +/- 1.0 and 1.2 +/- 1.5 vs 9.3 +/- 1.1 s of morphine alone, respectively), therefore displaying anti-opioid activity.5 In the Freund's adjuvant-induced rat model of arthritis, both NC and [F/G]NC(1-13)NH2 act as anti-opioid peptides. Furthermore, NCNH2 and [F/G]NC(1-13)NH2 induce hyperalgesia when given alone. Further investigations and the identification of a centrally acting ORL-1 antagonist are necessary to better understand the role of NC in pain mechanisms.