The peripheral role of group I metabotropic glutamate receptors on nociceptive behaviors in rats with knee joint inflammation

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 μM/25 μl, n = 10 per group) and selective mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP: 50, 100, 200 nM/25 μl, n = 10 per group) was intra-articularly (i.a.) injected 30 min before and 4 h 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 μM) 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 μM) 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 μM. 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.