Figure 9.

Systemic MEK inhibition attenuates formalin-induced spontaneous behaviors similarly in WT and ERK1 KO littermates. A, Several doses of the blood–brain barrier-permeant MEK inhibitor, SL327, or vehicle (DMSO) were administered intraperitoneally 30 min before hindpaw intraplantar formalin injection (3.5% in saline). Subjects (n = 3 per dose) were killed 3 min after formalin injection, and homogenates of spinal cord tissue ipsilateral and contralateral to the paw injection were analyzed for ERK phosphorylation. SL327 significantly reduced pERK1/ERK1 and pERK2/ERK2 at 30 and 50 mg/kg [one-way ANOVA with Dunnett's post test comparing to vehicle (0) within ERK isoform; **p < 0.01, ***p < 0.001]. B, ERK1 KO and WT mice were injected with either vehicle (1 ml/kg DMSO) or 50 mg/kg SL327 intraperitoneally (WT–vehicle, n = 9; WT–SL327, n = 11; KO–vehicle, n = 8; KO–SL327, n = 8). After 30 min, formalin (3.5% in saline) was injected subcutaneously into the plantar surface of the hindpaw, and spontaneous nociceptive behaviors were measured. SL327 significantly attenuated formalin-induced nociceptive behaviors in both WT and ERK1 KO littermates (two-way RM ANOVA with Bonferroni's post test; asterisks comparing WT–vehicle and WT–SL327, **p < 0.01, ***p < 0.001; daggers comparing KO–vehicle and KO–SL327, ^††p < 0.01). No significant difference was detected between WT and ERK1 KO mice injected with SL327.