Figure 1

Increased inhibitory potency of a group II mGluR agonist in the arthritis pain model. A: A selective group II mGluR agonist (LY354740; 1 nM, 12 min) has little inhibitory effect in a CeLC neuron recorded in a slice from a normal rat. B: In a CeLC neuron from an arthritic rat, LY354740 (1 nM, 12 min) strongly decreases the EPSC amplitude. A, B: Each trace is the average of 10 monosynaptic EPSCs evoked at the PB-CeLC synapse and recorded in whole-cell voltage-clamp at -60 mV (see Methods). C: LY354740 (1 μM) inhibited synaptic transmission in a CeLC neuron from a normal rat in the presence of bicuculline (20 μM) to block GABA_A receptors. Bicuculline alone had no apparent effect. D: The mean EPSC amplitude of CeLC neurons from arthritic rats (n = 13) was significantly higher compared to neurons from normal rats (n = 12, unpaired t-test), suggesting enhanced synaptic transmission (synaptic plasticity). E: Cumulative concentration-response relationships (see Methods) show that LY354740 inhibits synaptic transmission in CeLC neurons from arthritic rats more potently than in control neurons from normal rats (P < 0.01, F_1,45 = 7.89, two way ANOVA). IC₅₀s are 15.0 nM (normal) and 0.59 nM (arthritis). Peak amplitudes of EPSCs recorded at the PB-CeLC synapse during each concentration of LY354740 in neurons from normal rats (n = 9) and neurons from arthritic rats (n = 13) were averaged and expressed as percent of predrug (baseline) control (100%). LY354740 was applied by superfusion of the slice in ACSF for 12 min. Symbols and error bars represent mean ± SE. IC₅₀ values were calculated as described in Methods. * P < 0.05.