Lee Kyu Sang, Kim Junesun, Yoon Young Wook, Lee Min-Goo, Hong Seung Kil, Han Hee Chul
Department of Physiology, Brain Korea 21 Project for Medical Science, College of Medicine and Neuroscience Research Institute, Korea University, 126-1 Anam-dong 5 ga, Sungbuk-gu, Seoul 136-705, South Korea.
Neurosci Lett. 2007 Apr 12;416(2):123-7. doi: 10.1016/j.neulet.2007.01.063. Epub 2007 Feb 2.
We examined whether the mGluR1 and mGluR5 were involved in development and maintenance of behavioral signs of non-evoked pain and secondary mechanical hyperalgesia induced by knee joint inflammation. Selective mGluR1 antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA: 50, 100, 200 microM/25 microl, n=10 per group) and selective mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP: 50, 100, 200 nM/25 microl, n=10 per group) was intra-articularly (i.a.) injected 30 min before and 4h after carrageenan injection and behavioral tests were conducted. In the pre-treatment, only a higher dose (200 nM) of MPEP significantly prevented the magnitude of weight load reduction, whereas AIDA (200 microM) and MEPE (50, 100 and 200 nM) significantly reduced the development of mechanical hyperalgesia compared to saline treated group. In the post-treatment, AIDA (200 microM) and MPEP at 100 and 200 nM partially reversed the reduction of weight load induced by carrageenan. MPEP significantly increased the withdrawal threshold to mechanical stimulation in a dose-dependent manner, whereas AIDA had significantly reversed the decreased the paw withdrawal threshold only at 200 microM. The present study demonstrated that i.a. MPEP, selective mGluR5 antagonist is more effective than selective mGluR1 antagonist, AIDA on non-evoked pain as well as mechanical hyperalgesia in both induction and maintenance phase in knee joint inflammation. It is suggested that peripheral mGlu5 receptors play a more prominent role in inflammatory pain including evoked and spontaneous pain. Thus, selective mGluR5 antagonist could be effective therapeutic tools in clinical setting.
我们研究了代谢型谷氨酸受体1（mGluR1）和代谢型谷氨酸受体5（mGluR5）是否参与膝关节炎症诱导的非诱发性疼痛行为体征和继发性机械性痛觉过敏的发生及维持过程。在注射角叉菜胶前30分钟和注射后4小时，关节腔内（i.a.）注射选择性mGluR1拮抗剂（RS）-1-氨基茚满-1,5-二羧酸（AIDA：50、100、200微摩尔/25微升，每组n = 10）和选择性mGluR5拮抗剂2-甲基-6-（苯乙炔基）吡啶（MPEP：50、100、200纳摩尔/25微升，每组n = 10），随后进行行为学测试。在预处理中，仅较高剂量（200纳摩尔）的MPEP能显著预防体重负荷降低的程度，而与生理盐水处理组相比，AIDA（200微摩尔）和MPEP（50、100和200纳摩尔）能显著减轻机械性痛觉过敏的发展。在处理后，AIDA（两200微摩尔）以及100和200纳摩尔的MPEP能部分逆转角叉菜胶诱导的体重负荷降低。MPEP以剂量依赖方式显著提高对机械刺激的撤腿阈值，而AIDA仅在200微摩尔时能显著逆转爪撤腿阈值的降低。本研究表明，关节腔内注射选择性mGluR5拮抗剂MPEP在膝关节炎症的诱导期和维持期对非诱发性疼痛以及机械性痛觉过敏比选择性mGluR1拮抗剂AIDA更有效。提示外周mGlu5受体在包括诱发性和自发性疼痛在内的炎性疼痛中发挥更突出的作用。因此，选择性mGluR5拮抗剂可能是临床环境中有效的治疗工具。
