Fig. 5

Isotalatizidine exerts analgesic effect by increasing dynorphin A in the spinal cord tissue via the ERK1/2-CREB pathway. Isotalatizidine (1 mg/kg, n = 6) induced a time-dependent mechanical antiallodynia of ipsilateral paws in CCI-induced mice, which was completely prevented by ERK inhibitor of U0126-EtOH and CREB inhibitor of KG-501, but not p38 inhibitor of SB203580 (a). Phosphorylated level of ERK1/2 and CREB and expression of dynorphin A stimulated by isotalatizidine treatment could be blocked by U0126-EtOH or KG-501 in spinal dorsal tissue, respectively (b). Isotalatizidine treatment resulted in the releasing of dynorphin A in spinal cord tissue, which could be suppressed by U0126-EtOH or KG-501, but not SB230580 (c). Data are expressed as means ± SEM. ^*P < 0.05 vs. CCI mice; ^#P < 0.05 vs. isotalatizidine treated CCI mice. In cultured BV-2 cells, isotalatizidine-induced mRNA expression of prodynorphin also could be inhibited by U0126-EtOH or KG-501, but not SB230580 (d). Data are expressed as means ± SEM of three independent experiments. ^**P < 0.01 vs. control group; ^#P < 0.05 vs. isotalatizidine group