Glutamate receptor ligands attenuate allodynia and hyperalgesia and potentiate morphine effects in a mouse model of neuropathic pain
Glutamate receptor ligands attenuate allodynia and hyperalgesia and potentiate morphine effects in a mouse model of neuropathic pain
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DOI：
10.1016/j.pain.2008.03.017
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发表时间：
2008-09-30
期刊：
影响因子：
7.4
通讯作者：
Przewlocka, Barbara
中科院分区：
文献类型：
--
作者：
Osikowicz, Maria;Mika, Joanna;Przewlocka, Barbara
最近的研究表明，代谢性谷氨酸受体mGluR5、mGluR2/3和mGluR7存在于中枢神经系统中对伤害性传递很重要的区域，但它们在神经性疼痛中的作用尚未得到很好的证实。我们证明急性和慢性给药MPEP （mGluR5拮抗剂）、LY379268 （mGluR2/3激动剂）和AMN082 （mGluR7激动剂）减轻了瑞士白化小鼠坐骨神经慢性收缩损伤（CCI）后第7天的异常性疼痛（von Frey试验）和痛觉过敏（冷板试验）。此外，在吗啡前30分钟单次注射M PEP （30 mg/kg; i.p.）或LY379268 （10 mg/kg; i.p.）可增强吗啡在小鼠CCI模型中的作用（20 mg/kg; i.p.）。然而，单次给药AMN082 （3mg /kg; i.p）仅在von Frey试验中增强了单次吗啡注射（20mg /kg; i.p）的作用。慢性给药（7天）低剂量MPEP、LY379268或AMN082（所有药物均为3mg /kg， i.p）增强了第7天给药的单剂量吗啡（3,10和20mg /kg， i.p）的作用；而AMN082仅在冷板试验中增强了这一作用。此外，相同剂量的MPEP和LY379268（但不包括AMN082）长期与吗啡（40 mg/kg; i.p）共同给药，可以减弱cci暴露小鼠吗啡耐受的发展。我们的数据表明，mGluR5、mGluR2/3和mGluR7参与了损伤性损伤通路的可塑性改变，mGluR5和mGluR2/3配体增强了吗啡在神经病变中的有效性，这可能具有治疗意义。(C) 2008年国际疼痛研究协会。Elsevier B.V.版权所有。
Recent studies have indicated that metabotropic glutamate receptors mGluR5, mGluR2/3 and mGluR7 are present in the regions of central nervous system important for nociceptive transmission, but their involvement in neuropathic pain has not been well established. We demonstrated that acute and chronic administration of MPEP (mGluR5 antagonist), LY379268 (mGluR2/3 agonist), and AMN082 (mGluR7 agonist) attenuated allodynia (von Frey test) and hyperalgesia (cold plate test) as measured ill Swiss albino mice oil day seven after chronic constriction injury (CCI) to the sciatic nerve. Moreover, single administration of M PEP (30 mg/kg; i.p.) or LY379268 (10 mg/kg; i.p.) injected 30 min before morphine potentiated morphine's effects (20 mg/kg; i.p.) in the mouse CCI model, as measured by both the tests mentioned above. However, a single administration of AMN082 (3 mg/kg; i.p.) potentiated the effects of a single morphine injection (20 mg/kg; i.p.) in the von Frey test only. Chronic administration (7 days) of low doses of MPEP, LY379268 or AMN082 (all drugs at 3 mg/kg; i.p.) potentiated the effects of single doses of morphine (3, 10, and 20 mg/kg; i.p.) administered on day seven; however, AMN082 only potentiated the effect in the cold plate test. Additionally, the same doses of MPEP and LY379268 (but not AMN082) chronically co-administered with morphine (40 mg/kg; i.p.) attenuated the development of morphine tolerance in CCI-exposed mice. Our data suggest that mGluR5, mGluR2/3, and mGluR7 are involved in injury-induced plastic changes in nociceptive pathways and that the mGluR5 and mGluR2/3 ligands enhanced morphine's effectiveness in neuropathy, which could have therapeutic implications. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.