Analgesic Effect Of Tetramethylpyrazine On Neuropathic Pain Rats And Its Effects On Voltage Gated Calcium Channels In Dorsal Root Ganglion Neurons

Objective:The rat model of neuropathic pain was made by sciatic nerve ligation(SNL).In order to study the analgesic effect of tetramethylpyrazine on neuropathic pain,whether the neuropathic pain model will show depressive behaviors and whether tetramethylpyrazine has antidepressant effects on depressive symptoms associated with neuropathic pain,different doses of tetramethylpyrazine was given to detect the thermal withdrawl latency and mechanical withdrawl threshold and concomitant depressive behaviors in rats with neuropathic pain.The effects of tetramethylpyrazine on calcium current in dorsal root ganglion were examined by whole cell patch clamp technique.The mechanism of analgesia of tetramethylpyrazine was explored from the perspective of calcium channels.Methods:50 healthy adult male Sprague-Dawley rats,weight 180-220g,were randomly divided into 5 groups:Sham group(control),DMSO group(model)and low dose tetramethylpyrazine group,medium dose tetramethylpyrazine group and high dose tetramethylpyrazine group,10 in each group.In Sham group rats sciatic nerve were exposed only,but not ligated,in DMSO,low dose tetramethylpyrazine group,medium dose tetramethylpyrazine group and high dose tetramethylpyrazine group rats sciatic nerve ligation(SNL)method was adopted to establish the neuropathic pain model.tetramethylpyrazine group rats after SNL began to be given tetramethylpyrazine through intraperitoneal injection,1 time/day,low dose group 10mg/kg,medium dose group 20mg/kg,high dose group 40mg/kg,until to the day of death;Sham group rats were injected with normal saline instead,DMSO group with equal volume of 3%DMSO instead.Mechanical withdrawl threshold and thermal withdrawl latency of each group of rats were measured on the first day before operation,3rd day after operation,7th day after operation,14th day after operation,30th day after operation,The effects on depressive behaviors were measured on the 15th day after operation,19th day after operation,21 st day after operation and 23rd day after operation,by sugar water preference,open field experiment,forced swimming test,food consumption test.Also taking normal rats,scattered dorsal root ganglion(DRG)acutely,recorded the ?-? curve of DRG calcium current,the activation curve,the inactivation curve,the concentration curve,and the non L-calcium current with whole cell patch clamp technique to analyze the effect of tetramethylpyrazine on DRG calcium currents.Results:Compared with DMSO group,low dose,middle dose,and high dose of tetramethylpyrazine can increase thermal withdrawl latency,but only high dose of tetramethylpyrazine can increase mechanical withdrawl threshold.The SNL neuropathic pain model show no depressive behaviors.Tetramethylpyrazine has no effect on depressive behaviors of neuropathic pain rats.Tetramethylpyrazine can also dose-dependently inhibit ?-? curve,activation curve of calcium current in DRG,inhibit non L-type calcium current,but has no effect on the inactivation curve.Conclusion:Tetramethylpyrazine can play an analgesic effect on neuropathic pain rats,which mechanisms may be related to inhibiting effect on DRG calcium current.