The Role Of The Alteration Of GABA Transporter 3 In The Injured Drg In The Etiology And Development Of Neuropathic Pain

Background:Neuralgia is very common in the clinic,and the mechanism is still unclear.There is still no effective treatment.Increased sensitivity of the nervous system is an important mechanism of neuralgia.In recent years,it has been found that the GABA reuptake system,GABA transporter,may be involved in various pain processes.Studies have shown that GAT1 in the dorsal horn of the spinal cord is significantly increased after nerve injury,and intrathecal injection of GAT1 inhibitor NO711 can significantly relieve the symptoms of neuralgia.Studies have confirmed that there is GAT3 expression in the dorsal root ganglia,but whether GAT3 changes after nerve injury,whether these changes are related to the occurrence of neuralgia,there is no research involved.Objective: To explore the expression of GAT3 in dorsal root ganglion after nerve injury and its role in the occurrence and development of neuralgia.Methods:SD rats were used to make chronic constriction injury(CCI)model.The paw withdrawal latency(PWL)was measured after operation to verify the success of the model by comparing operative side with non-operative side.On the 3rd day and the 7th day after operation,the expression of GAT3 protein and m RNA in L4-L5 DRG of Sham group and CCI group were detected by western blot and real-time PCR.On the 3rd day and the 7th day after operation,GAT3 inhibitor SNAP511(200 μg,10 μl)was injected into the SNAP group through catheters that pre-implanted on L5 DRG,while DMSO(10 μl)was injected into CCI group.The changes of PWL were measured.Results:Compared with the Sham group,the PWL in the CCI group was significantly shorter than that in the Sham group(P < 0.05).Compared with the Sham group,On the 3rd day after operation,the expression of GAT3 protein in L4-L5 DRG was significantly increased in the CCI group(P < 0.05),On the7 th day after operation,the expression of GAT3 protein was decreased(P < 0.05).The results of RT-PCR also showed that on the 3rd day the expression of GAT3 m RNA in DRG was significantly increased(P < 0.05),on the 7th day,the expression of GAT3 m RNA was decreased(P < 0.05).Behavioral study showed that on the 3rd day after operation,PWL in SNAP group was significantly longer than that in CCI group,and the effects maintain for 24hours(P < 0.05),but on the 7th day after operation,PWL in SNAP group was no significant change(P > 0.05).Conclusion:The expression of GAT3 in the dorsal root ganglia changes after nerve injury.L5 DRG topical GAT3 inhibitor can only transiently alleviate the symptom of neuropathic pain,which means changes of GAT3 of L5 DRG is not the main factor for the occurrence of neuropathic pain.