흰쥐의 CFA로 유도한 무릎관절통에 대한 중추에서의 Group I mGluRs의 역할.

초록

BACKGROUND Glutamate is the predominant excitatory neurotransmitter in the central and peripheral nervous system and has known to be involved in nociceptive transmission and central sensitization. It acts through ligand gated ionotropic glutamate receptors (iGluRs) and G protein-coupled metabotropic glutamate receptors (mGluRs). And mGlu 1, 5 receptors have been recognized to play a role in nociceptive processing. We want to investigate whether central mGluR1 and mGluR5 antagonists could reverse the behavioral signs of weight bearing and secondary mechanical hyperalgesia induced by chronic knee joint inflammation. METHODS MGluR1 antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA: 25, 50, 100 microM/10 microliter, n = 7 per group) and selective mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP: 25, 100, 200 nM/10 microliter, n = 7 per group) were injected intrathecally 5 days after Complete Freund's Adjuvant (CFA, 150 microliter) injection into knee joint and behavior signs of weight bearing and secondary mechanical hyperalgesia were observed. RESULTS CFA significantly reduced the magnitude of right hind paw weight bearing and decreased the withdrawal threshold to mechanical stimulation compared to contralateral side. Higher dose of AIDA (100 microM) significantly reversed the reduction of weight bearing, but MPEP did not. AIDA reversed the decrease of the paw withdrawal threshold to mechanical stimulation at the dosage of 50 and 100 microM respectively. MPEP significantly increased the paw withdrawal threshold to mechanical stimulation in a dose dependent manner. CONCLUSIONS Group I mGluRs were involved in maintenance of primary and secondary mechanical hyperalgesia.

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