Figure 4

SCDH atypical PKC expression, and effects of PKMζ/PKC inhibition on spinal DHPG-induced allodynia. (a) Spike rate (spikes/sec) of evoked responses of a WDR neuron to 20 and 50 g von Frey filaments before and 5 or 25 min after DHPG. Note the increased evoked responses to both mechanical stimuli, and the prolonged after-discharges to the 50 g stimulus, both 5 and 25 min post-DHPG. Scale bar (20 sec). (b) Western blots and (c) histograms of % change in atypical PKC levels compared to vehicle illustrating that i.t. DHPG significantly increased PKMζ (n = 12), but not PKCζ (n = 12) or PKCι/λ (n = 8) in SCDH (vehicle, n = 11), 2 and 24 h post-DHPG combined (*P < 0.05). (d,e) Pre- and post-DHPG paw withdrawal thresholds (PWTs, g) for rats given i.t. ZIP or scr-ZIP (d), i.t. NPC-15437 or vehicle (e), 30 min prior to testing at 24 h post-DHPG, with additional testing 48 h post-drug. ZIP (*P < 0.05), but not scr-ZIP or NPC-15437, reversed DHPG-induced mechanical allodynia at both time-points (n = 5 for each drug). f) Pre-drug (base) and post-drug PWTs of CCI rats (n = 8), early CPIP rats (n = 9) and late CPIP rats treated with i.t. ZIP (n = 7), or late CPIP rats treated with i.t. scr-ZIP (n = 8). ZIP, but not scr-ZIP, reversed allodynia in late CPIP rats, while ZIP had no effects in CCI or early CPIP rats (* P < 0.01; ** P < 0.001 from scr-ZIP; † P < 0.05; †† P < 0.01 from pre-drug baseline).