| objective: trigeminal neuralgia(TN)is a severe pain occurring in the distribution area of trigeminal nerve,which is a common facial neuralgia.The exact mechanism,however,is still unclear.The recent studies have indicated that the damage of nigrostriatal dopaminergic neurons also exert great influence in the pathogenesis of TN,moreover the C-Abl-p38 signaling played a crucial role in dopaminergic neuron death,from which we could infer that c-Abl-p38 signal may have an important role in TN.The study wanted to provide a theoretical basis for the search of molecular targets for TN therapy,by exploring the effect of c-Abl and its inhibitors on TN in rat TN model,and the relationship between c-Abl and p38 signal transduction pathway in TN.Method: 1.animal models:60 adult male SD rats were undergone a 7-day adaptive training before operation,and then the rats whose pain threshold were greater than 26 g for 3 days while having complete hair tentacles in the mouth and nose were randomly divided into four groups(n=15): Sham group(group A): the suborbital nerve was separated only without ligation.Operation group(group B): actualizing right ION constriction injury.Operation group+inhibitor(group C): actualizing right ION constriction injury+C-abl inhibitor(imatinib mesylate STI571);Operation group+saline water(group D): actualizing right IONconstriction injury+saline water.The mechanical pain threshold of the right infraorbital facial innervation area of the rats was continuously evaluated within 7 days after operation,whose pain threshold of 3consecutive days less than 6 g was considered to be successful in the establishment of the model.2.Pain threshold detection:Four groups of rats(n=5)were treated with different dynamics Von Frey filaments to stimulate the right suborbital nerve in the innervation area of the face,the mechanical pain threshold was measured and recorded at 1 day,3 days,7days,8 days,9 days,14 days and 21 days and 28 days after operation.3.Detection of c-Abl?p38?p-p38?TH protein:Western blotting and paraffin section immunofluorescence were used to detect the expression and location of c-Abl,p38,p-p38 and TH protein in the striatum of rats on the 14 th day after operation.Results: 1.1.Modeling result: To eliminate 2 rats were hyperalgesia before operation,5 rats died during the experiment,4 rats did not appear hyperalgesia after operation,71 rats were used in this experiment,and a total of 60 rats were included in this study.2.Comparison of pain threshold in rats:Comparison in the group:The pain threshold of the four groups was 26 g on the 1d,3d,before operation.There was no significant difference in pain threshold at each time point in group A(P>0.05).In group B and D,the pain threshold of pre-operation,1d and 3d was higher than that of 7d,8d,9d,14 d,21d,28d(P<0.05);The data of 7d,8d,and 9d are lower than that of 21 d and 28d(P<0.05);and 14d(0.56 + 0.26g)was the lowest,lower than that of pre-operation,1D,3D,7d,8D,9D,21 d,28d(P<0.05),other than that,there was no statistical significance at other time points(P>0.05).Comparison between two groups: the pain threshold of 7d?8d?9d?14d?21d?28d of group B and D were lower than that of group A(P<0.05),as well as group C(P<0.05);the pain threshold of 8d?9d?14d?21d of group C were lower than that of group A(P < 0.05),while the 7d's of group C was lower than group A's(P > 0.05).3.Detection of c-Abl?p38?p-p38?TH protein: The expression of C-Abl?p-p38 in group B and D was significantly higher than that in group A and C(P<0.05).The expression of TH in group B and D was lower than that in group A and C(P>0.05).The expression of C-Abl,p-p38 and TH were no significant difference between group A and group B,C and D(P>0.05).The expression of C-Abl?p-p38 and TH were detected by immunofluorescence in all four groups,mainly on the cell cytoplasm,peculiar flaky structure of the striatum.There was no significant difference in the expression of p38 between the four groups(P>0.05).The expression of p38 was detected by immunofluorescence in all four groups,mainly on the cell nucleus,cell cytoplasm,peculiar flaky structure of the striatum.Conclusion: 1.The expression of c-Abl protein in striatum of rats with trigeminal neuralgia increased,and the threshold of pain would increase accompanied by the decreasing c-Abl protein after using c-Abl inhibitor,suggesting that c-Ablprotein might be involved in the pathogenesis of trigeminal neuralgia.2.The expression of p-p38 protein in striatum of rats with trigeminal neuralgia increased,and it decreased after using c-Abl inhibitor,indicating that c-Abl-p38 pathway play an important role in the occurrence and development of trigeminal nerve.3.The expression of TH protein in striatum of rats with trigeminal neuralgia decreased,and then increased after using c-Abl inhibitor.It is suggested that the activation of c-Abl in trigeminal neuralgia rats may reduce TH and cause the injury of dopaminergic neurons.C-Abl-p38 pathway is activated and involved in the pathogenesis of TN through the injury of dopaminergic neurons. |
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