Mechanism of alleviating neuropathic pain in rats by inhibiting the expression of P38MAPK signaling pathway
Objective To explore the mechanism of alleviating neuropathic pain in rats by inhibiting the expression of P38 mitogen-activited protein kinase(P38MAPK)signaling pathway.Methods Sixty male specific pathogen-free(SPF)grade rats were selected(body weight 200-220 g,about 3 months old),among them 10 rats were randomly selected as a sham operation group,and the remaining rats were used to establish a chronic compressive injury(CCI)model.The rat models[the success rate of modeling was 80%(40/50)]were randomly divided into a model group and a P38MAPK inhibitor group.On the 6th day after modeling,normal saline and P38MAPK inhibitor were injected into the sheath twice a day for consecutive 5 days.The mechanical pain threshold and motor function score of the rats in each group were measured 1,7 and 11 days after operation.The rats were euthanized on the 11th day after operation,and the expressions of P38MAPK and cyclooxygenase-2(COX-2)protein in the dorsal root ganglia of the rats were determined by the immunohistochemical method.The measurement data were analyzed by repeated measure ANOVA.Results There was no significant change in the mechanical pain threshold in the sham operation group;the pain threshold level of the model group significantly decreased on the 7th day and to the lowest level on the 11th day after operation;the pain threshold level in the P38MAPK inhibitor group decreased on the 7th day and significantly increased on the 11th day after operation(P<0.05),which was higher than that in the model group(P<0.05).The model group and the P38MAPK inhibitor group showed significant motor dysfunction on the 7th day after operation;the degree of motor dysfunction in the model group increased on the 11th day,but the degree of motor dysfunction in the P38MAPK inhibitor group decreased on the 11th day(P<0.05),whose motor function score was lower than that of the model group(P<0.05).The expression of P38MAPK immune positive cells in the sham operation group was lower than that in the P38MAPK inhibitor group and lower than that in the model group[(7.35±0.63)%vs.(25.36±1.85)%vs.(60.23±2.17)%](P<0.05);the expression of COX-2 protein-positive cells in the sham operation group was lower than that in the P38MAPK inhibitor group and lower than that in the model group[(5.21±2.23)%vs.(15.14±2.01)%vs.(33.43±3.02)%](P<0.05).Conclusion The P38MAPK signaling pathway is related to the occurrence of neuropathic pain,and inhibiting the expression of P38MAPK signaling pathway can alleviate neuropathic pain in rats.