Figure 4.

Enhancement of C-fiber-evoked spinal field potentials that is promoted by 5-HT_2AR after SNL is mediated by mGluR1, but not by mGluR2/3 or NMDA. Preliminary experiments to determine the effects of pharmacological blockade of mGluR1, mGluR2/3, and the NMDA receptor in nerve-ligated rats are shown in A. Administration of NMDA receptor antagonist d-AP5 at 100 μm significantly decreased mean evoked potential areas, and thus a 10 μm concentration was considered as subclinical for further experiments, whereas 10 and 100 μm concentrations were selected for mGluR1 antagonist AIDA and for group II mGluR antagonist LY 341495, respectively. Mean areas of C-fiber-evoked potentials are shown in B during spinal superfusion with increasing, cumulative concentrations of 5-HT_2AR agonist TCB-2 (100 μm) either alone (open triangles) or in combination with subclinical concentrations of AIDA (solid triangles), LY341495 (open circles), or d-AP5 (solid circles). Coadministration of neither LY341495 nor d-AP5 altered the ability of TCB-2 to augment evoked field potentials in nerve-ligated rats. In contrast, coadministration of AIDA increased the minimal effective concentration of TCB-2 by 3 orders of magnitude and dramatically increased the EC₅₀ of TCB-2. Statistical significance (p < 0.01 at Bonferroni's test) of increases in field potential areas by effect of TCB-2 relative to baseline controls in the absence or presence of AIDA is denoted by asterisks or section signs, respectively. Representative recordings shown at the top illustrate the enhancing effect of 100 μm TCB-2 on C-fiber-evoked field potentials in the absence (a) or concurrent presence of 10 μm AIDA (b). Error bars indicate SEM.