SCDH atypical PKC expression, and effects of PKMζ/PKC inhibition on formalin nociception. (a) Western blots and (b) histograms (% change) of atypical PKC showing i.pl. formalin increased PKMζ, PKCζ and PKCι/λ (n = 5/6 for vehicle/formalin) in SCDH (*P < 0.05). (c) Effect of ZIP on rotarod latencies, which significantly increased over training (*p < 0.05 from day 1). Latencies on day 6 (after ZIP) did not differ from day 5 (n.s.: non-significant difference). (d,e) Dose-dependent effects of pretreatment with ZIP (n = 5-7/dose) vs. scr-ZIP (n = 7) (d) or NPC-15437 (n = 5-7/dose) vs. vehicle (n = 8) (e) on formalin pain. ZIP dose-dependently reduced late phase (9-45 min) scores (†P < 0.05, *P < 0.01 red dash-boxed or individual symbols from scr-ZIP), but not early phase scores (0-6 min). NPC-15437 also significantly reduced late phase scores (†P < 0.05, *P < 0.01 for red dash-boxed or individual symbols), but not early phase scores. (f,g) Effect of ZIP (n = 6) or scr-ZIP (n = 4) pretreatment on von Frey paw-withdrawal thresholds (PWT, f) or plantar test paw-withdrawal latencies (PWL, g) in naïve rats. Neither ZIP nor scr-ZIP significantly affected either PWTs or PWLs. (h,i) Painful responses induced by formalin before and after ZIP (n = 5) or scr-ZIP (n = 5) (h), and NPC-15437 (n = 5) or vehicle (n = 7) (i), administered 25 min post-formalin. ZIP (*P <.05), but not NPC-15437, significantly attenuated persistent formalin pain. For these and subsequent graphs ZIP, scr-ZIP, NPC-15437 and vehicle were given i.t., and data is expressed as means ± s.e.m. unless otherwise stated.