Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice
Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice
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DOI：
10.1016/j.pbb.2011.05.029
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发表时间：
2011-10-01
影响因子：
3.6
通讯作者：
Ulugol, Ahmet
中科院分区：
文献类型：
--
作者：
Gunduz, Ozgur;Karadag, Hakan C.;Ulugol, Ahmet
不同类别的止痛药组合通常用于慢性疼痛的治疗。其目标是在减轻疼痛的同时减少副作用。本研究旨在探讨大麻素CBI受体激动剂Win 55,212-2与伤害素/孤儿FQ受体拮抗剂JTC-801合用对神经病理性疼痛的抗痛觉过敏性协同作用。在手术前和术后2-4周对小鼠进行行为效应测试，其中部分结扎坐骨神经。用动态足底感觉仪评估神经损伤所致的机械性痛觉异常，用冷热平板评估冷痛感。Win 55、212-2和JTC-801均表现出剂量依赖性的机械和冷抗痛觉异常作用。同源分析表明，Win 55、212-2/JTC-801组合在机械性痛觉过敏试验中所研究的所有三个比例下都具有协同作用。综上所述，大麻素与伤害素/孤儿FQ受体拮抗剂联合给药可产生协同作用，这可能在神经病理性疼痛的药物治疗中有应用价值。(C)2011 Elsevier Inc.保留所有权利。
Combinations of analgesics from different classes are commonly used in the management of chronic pain. The goal is to enhance pain relief together with the reduction of side effects. The present study was undertaken to examine the anti-allodynic synergy resulting from the combination of WIN 55,212-2, a cannabinoid CBI receptor agonist, and JTC-801, a nociceptin/orphanin FQ receptor antagonist, on neuropathic pain. Mice were tested for behavioral effects before and 2-4 weeks after the surgery, in which a partial tight ligation of the sciatic nerve was made. Nerve injury-induced mechanical allodynia was assessed with Dynamic Plantar Aesthesiometer, and a hot/cold plate was used to assess cold allodynia. Both WIN 55,212-2 and JTC-801 produced dose-dependent mechanical and cold anti-allodynic effects. As shown by isobolographic analysis, WIN 55,212-2/JTC-801 combinations interacted synergistically at all three ratios studied in the mechanical allodynia assay. In conclusion, co-administration of a cannabinoid with a nociceptin/orphanin FQ receptor antagonist resulted in a synergistic interaction, which may have utility in the pharmacological treatment of neuropathic pain. (C) 2011 Elsevier Inc. All rights reserved.