Osikowicz Maria, Mika Joanna, Makuch Wioletta, Przewlocka Barbara
Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
Pain. 2008 Sep 30;139(1):117-126. doi: 10.1016/j.pain.2008.03.017. Epub 2008 Apr 28.
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 in Swiss albino mice on day seven after chronic constriction injury (CCI) to the sciatic nerve. Moreover, single administration of MPEP (30 mg/kg; i.p.) or LY379268 (10mg/kg; i.p.) injected 30 min before morphine potentiated morphine's effects (20mg/kg; i.p.) in the mouse CCI model, as measured by both the tests mentioned above. However, a single administration of AMN082 (3mg/kg; i.p.) potentiated the effects of a single morphine injection (20mg/kg; i.p.) in the von Frey test only. Chronic administration (7 days) of low doses of MPEP, LY379268 or AMN082 (all drugs at 3mg/kg; i.p.) potentiated the effects of single doses of morphine (3, 10, and 20mg/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.
近期研究表明，代谢型谷氨酸受体mGluR5、mGluR2/3和mGluR7存在于对伤害性感受传递至关重要的中枢神经系统区域，但它们在神经性疼痛中的作用尚未完全明确。我们证明，在对瑞士白化小鼠坐骨神经进行慢性缩窄损伤（CCI）后第7天，急性和慢性给予MPEP（mGluR5拮抗剂）、LY379268（mGluR2/3激动剂）和AMN082（mGluR7激动剂）可减轻异常性疼痛（von Frey试验）和痛觉过敏（冷板试验）。此外，在小鼠CCI模型中，在吗啡（20mg/kg；腹腔注射）给药前30分钟单次给予MPEP（30mg/kg；腹腔注射）或LY379268（10mg/kg；腹腔注射），上述两种试验均显示可增强吗啡的作用。然而，单次给予AMN082（3mg/kg；腹腔注射）仅在von Frey试验中增强了单次吗啡注射（20mg/kg；腹腔注射）的作用。低剂量的MPEP、LY379268或AMN082（所有药物均为3mg/kg；腹腔注射）慢性给药（7天）可增强第7天给予的单剂量吗啡（3、10和20mg/kg；腹腔注射）的作用；然而，AMN082仅在冷板试验中增强了该作用。此外，相同剂量的MPEP和LY379268（但不包括AMN082）与吗啡（40mg/kg；腹腔注射）长期联合给药可减轻CCI暴露小鼠吗啡耐受性的发展。我们的数据表明，mGluR5、mGluR2/3和mGluR7参与了伤害性感受通路中损伤诱导的可塑性变化，并且mGluR5和mGluR2/3配体可增强吗啡在神经病变中的有效性，这可能具有治疗意义。
