| Objective: This study focus on the role of MIF/ERK signaling pathway to allodynia in rat model of complex regional pain syndrome type 1(CRPS1) and its identify possible key mechanism that treatment by resveratrol.Methods: Part I. 30 adult male SD rats were randomly assigned to normal control group, sham-operated group, and chronic post-ischemia pain(CPIP) group respectively, with 10 rats in each group. After modeling, pain behaviors were observed at 1 hour, 8 hours, 24 hours, 48 hours, 3 days, 4 days, 7 days and 14days;serum level of MIF and TNF-α were detected by ELISA at 8 hours, 7 days and14 days. Finally, MIF, total ERK1/2 and p-ERK1/2 in sciatic nerve were detected by Western blotting. Part II. 50 adult male SD rats were randomized into normal control group(A group, n=10), sham-operated group(B group, n=10), model control group(C group, n=10), ISO-treated group(D group, n=10) and Res-treated group(E group,n=10). A, B, C groups were given daily intraperitoneal injection of each with 5%DMSO10μl, D group were given with ISO-1 dissolved in 5% DMSO 10 ul at 1mg/(kg·d), E group were given with Res dissolved in 5% DMSO 10 ul at 20mg/(kg·d), each rat was given 14 days of continuous treatment. Pain behaviors were tested, and serum level of MIF and TNF-α were detected by ELISA at day 0, day 7and day 14 in treatment. MIF, total ERK1/2 and p-ERK1/2 in sciatic nerve were detected by Western blotting at day 14 in treatment.Results: Part I. Spontaneous pain behavior and Q-tip test positive reaction appeared in CPIP group at 1 hour, 8 hours and 24 hours, but normal control group and sham-operated group without(P<0.05). Pain threshold of rats in CPIP group decreased obviously after modeling(P<0.05). The expression of serum MIF in CPIP group were significantly higher than normal control group and sham-operated group(P<0.05) throughout the observation point. The TNF-α were significantly higher in CPIP group(P<0.05) only at 8 hours and 7 days, no significant difference was found in three groups after 14 days about TNF-α(P>0.05). Western blotting showed theprotein of MIF, p-ERK1/2 were highly expressed in CPIP group. Part II. Pain threshold were significantly lower in C, D and E group(P<0.01), at day 0 in treatment. Day 7 in treatment, pain threshold were significantly improved in D, E group than C group(P<0.05), but still lower than A, B group(P<0.05). Day 14 in treatment, pain threshold were no significantly difference in D, E and A, B group(P>0.05), but significantly higher than C group(P<0.01). Serum level of MIF in C group were significantly higher than A, B group always(P<0.01). Day 0 in treatment, serum level of MIF in D, E group were significantly higher than A, B group(P<0.01), but day 7 and day 14 in treatment, MIF in D, E group were significantly lower than C group(P<0.05), there were no significantly difference in A, B, D, E group(P>0.05). day 0 in treatment. Serum level of TNF-α in C, D, E group were significantly higher than A group(P<0.01), day 7 in treatment, TNF-α in D, E group were significantly lower than C group(P<0.05), there were no significantly difference in A, B, D, E group, but day 14 in treatment, all treated groups had no significantly difference about TNF-α(P>0.05). Finally, MIF and p-ERK1/2 in D, E group were significantly lower than C group, there were no significantly difference in A, B, D, E group.Conclusion:1 MIF and ERK1/2 phosphorylation may participate in the molecular regulatory mechanism about CRPS1 pathological processes of allodynia.2 After inhibit MIF, p-ERK1/2 levels corresponding decreased, MIF may affect the process in CRPS1 allodynia by MAPK/ERK1/2 pathway.3 Similar to ISO-1, resveratrol can decrease the expression of MIF and p-ERK1/2 level in CRPS1 rat model.4 It suggests that resveratrol may play an important role in treatment of CRPS1 by inhibit ERK pathway. |
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