Fig. 4.

Paeoniflorin prevented neuropathic pain-associated allodynia and hyperalgesia. a, b Single administration of paeoniflorin (20, 40, and 60 mg/kg, i.p.) was administered at day 14 after CCI surgery, and paeoniflorin (40 and 60 mg/kg, i.p.) increased the mechanical and thermal thresholds in the ipsilateral paws of rats at 2, 4, and 8 h. Paeoniflorin (20 mg/kg, i.p.) increased the mechanical and thermal thresholds at 2 h (n = 8). c, d Consecutive administration of paeoniflorin (40 mg/kg, i.p.) significantly increased the mechanical and thermal thresholds in the ipsilateral paws up to day 21 after five times administration (n = 8). e, f Paeoniflorin (40 mg/kg, i.p.) significantly delay the development of neuropathic pain (n = 8). g, h Paeoniflorin (40 and 60 mg/kg, i.p.) decreased the phosphorylation of p38 and JNK but not ERK induced by CCI surgery (n = 4). i The effects of paeoniflorin and NQDI1 on mechanical and thermal thresholds in naive rats were measured. The lumbar spines (L1–L6) were collected and analyzed 2 h after the drug administration. PF, paeoniflorin. Significant differences were revealed following one-way ANOVA (*P < 0.05, **P < 0.01, ***P < 0.001 vs. control; ^#P < 0.05, ^##P < 0.01, ^###P < 0.001 vs. CCI group; Bonferroni post hoc tests)