Effects of PKMζ inhibition on capsaicin-induced sensitization of spinal WDR neurons. (a,b) Spike rate (spikes/sec) of evoked responses of 2 WDR neurons to von Frey filaments pre- and post-capsaicin. ZIP (90 min post-capsaicin) reduced the capsaicin-induced sensitization of mechanically-evoked responses of the neuron in (a). The neuron in (b) was not sensitized by capsaicin, and ZIP did not reduce evoked responses to the mechanical stimuli. (c-e) Mechanically-evoked WDR neuron responses to 1 (c), 5 (d) or 20 (e) g stimuli pre- and post-capsaicin (% of baseline action potentials evoked/20 s). ZIP, but not scr-ZIP (n = 6, 5, respectively), significantly reversed capsaicin-enhanced evoked responses to 5-20 g stimuli at 30-60 min post-drug (*P < 0.05). (f-h) Mechanically-evoked WDR neuron responses to 1 (f), 5 (g) or 20 (h) g stimuli pre- (baseline, BL) and post-vehicle (before (Veh) and after ZIP (30-60 min) applied 90 min post-vehicle) (n = 5). Neither i.pl. vehicle, nor i.t. ZIP, significantly affected evoked responses of WDR neurons. i) Background activity and evoked responses to heat pre- and post-capsaicin. Although capsaicin significantly increased the background activity of WDR neurons (** P < 0.01 from Pre-capsaicin), it failed to increase their heat-evoked responses (P > 0.05, n = 8). j) Background activity of WDR neurons pre- (baseline, BL) and post-capsaicin (before (Cap) and after ZIP (30-60 min) applied 90 min post-capsaicin, n = 6). Capsaicin significantly increased background activity (*P < 0.05), and ZIP failed to significantly reduce the capsaicin-induced increase in the background activity of WDR neurons (P > 0.05).