FIGURE 7.

Spinal JP-1302 does not affect wide dynamic range (WDR) cell activity, but behaviorally, it inhibits nociception by increasing GABAergic activity. (A,B) depict the peri-stimulus time histogram (PSTH) constructed from 20 WDR responses to receptive field (RF) electrical stimulation before (basal) and after treatment (vehicle or JP 1302); also, in these panels, the raster plot and raw tracing of a single second-order WDR neuron cluster response elicited by one electrical stimulus (upper tracing) are illustrated. In accordance with the fiber conduction velocities, the panels in the figure depict the different fiber components (Aβ-, Aδ-, and C-fibers) of the spinal WDR cell response. Note that JP 1302 seems not to exert an effect on the WDR neuronal activity; indeed, when the data are analyzed as a percent of change of the neuronal activity (C–F), JP 1302 does not impact (statistically) the neuronal firing associated with the activation of Aβ-, Aδ-, C-fibers, and post-discharge. (G) shows the effect of intrathecal (i.t.) injection of 0.3 nmol bicuculline (a preferent GABA_A receptor blocker) on the JP 1302-induced inhibition of the flinches induced by formalin (1%; 50 μl, s.c.) during phase I (P1) and phase II (P2). Note that bicuculline per se did not affect formalin-induced flinching behavior, but this GABA_A channel blocker reversed the effect of JP 1302. (H,I) represent the data as the area under the mean number of flinches against the curve (AUC) and show that bicuculline inhibited the JP 1302-induced antinociception in both phases (P1, P2).