蛛网膜下腔内注射TSA对RTX诱导神经病理性疼痛的影响及机制

Effects of subarachnoid injection of TSA on RTX-induced neuropathic pain and its mechanism

目的探讨蛛网膜下腔内注射古菌素A(TSA)对树酯毒素(RTX)诱导的神经病理性疼痛的影响及机制。方法雄性健康SD大鼠24只,用随机数字表法均分成Vehicle组、RTX组、RTX+DMSO组、RTX+TSA组。除Vehicle组外均进行神经病理性疼痛造模处理,并于建模前1周对RTX+DMSO组及RTX+TSA组进行蛛网膜下腔置管。Vehicle组单次腹腔注射RTX的溶媒1.5 m L;RTX组单次腹腔注射RTX 210μg/kg;RTX+DMSO组建模前60 min及建模后每天蛛网膜下腔内注射5%的DMSO 10μL,连续注射7 d;RTX+TSA组建模前60 min及建模后每天蛛网膜下腔内注射TSA 0.5μg/kg,其溶媒为5%的DMSO。建模前各组大鼠采用von Frey丝检测后肢足底基础痛阈值,建模后第1、3、5、7天测定机械痛阈值。于最后1次蛛网膜下腔内注射后2 h取材,采用qRT-PCR方法测定脊髓及脊神经背根节脑源性神经营养因子(BDNF)mRNA的表达。结果与Vehicle组相比,RTX组、RTX+DMSO组、RTX+TSA组在建模后第3、5、7天,机械痛阈值降低(P均<0.05);与RTX组和RTX+DMSO组相比,RTX+TSA组第5、7天建模机械痛阈值升高(P均<0.05);RTX组与RTX+DMSO组各时点相比,P均>0.05。与Vehicle组相比,RTX组和RTX+DMSO组脊髓及脊神经背根节BDNF mRNA表达下调(P均<0.05);与RTX组和RTX+DMSO组比较,RTX+TSA组脊髓及脊神经背根节BDNF mRNA表达上调(P均<0.05);RTX组与RTX+DMSO组相比,P均>0.05。结论蛛网膜下腔内注射TSA可通过上调BDNF的表达缓解RTX诱导的大鼠神经病理性疼痛。

Objective To study the effects of subarachnoid injection of trichostatin A（ TSA） on resiniferatoxin（ RTX）-induced neuropathic pain in rats and its mechanism. Methods Twenty-four male SD rats were randomly divided into four groups（ n = 6） ： Vehicle group,RTX group,RTX ＋ DMSO group,and RTX ＋ TSA group. The models of neuropathic pain were established in the remaining three groups except Vehicle group. Subarachnoid catheterization was performed in the RTX ＋ DMSO group and RTX ＋ TSA group one week prior to modeling. Before the establishment of the models,the rats were sacrificed with von Frey filaments to detect the basal value of the pain,and the mechanical pain threshold was measured on the 1st,3rd,5th,and 7th days after modeling. Vehicle group was treated with a single peritoneal RTX solvent 1. 5 m L; rats in the RTX group received intraperitoneal injection of RTX（ 210 μg/kg）; from 60 min before RTX injection,5% DMSO（ 10 μL） was injected into rats of the RTX ＋ DMSO group intrathecally once a day for 7 days; from60 min before RTX injection,TSA（ 0. 5 μg/kg） with solvent of 5% DMSO was injected into rats of the RTX ＋ TSA group intrathecally once a day. The expression of BDNF mRNA in the spinal cord（ SC） and dorsal root ganglion（ DRG） was measured by qRT-PCR at 2 h after last time of TSA injection. Results Compared with the Vehicle group,the RTX group,RTX ＋ DMSO group,and RTX ＋ TSA group displayed a significantly decrease in mechanical allodynia on the 3th,5th,and7 th days（ P 0. 05）. Compared with the RTX group and RTX ＋ DMSO group,the RTX ＋ TSA group had significantly higher mechanical pain threshold on 5th and 7th days（ all P 0. 05）. There was no statistically significant difference between the RTX group and RTX ＋ DMSO group（ P 0. 05）. Compared with the Vehicle group,the expression of BDNF mRNA was down-regulated in the spinal cord and DRG in the RTX group and RTX ＋ DMSO group（ P 0. 05）. Compared with the RTX group and RTX ＋ DMSO group,the expression of BDNF mRNA in the spinal cord was up-regulated in the RTX ＋ TSA group（ P 0. 05）. There was no statistically significant difference between the RTX ＋ DMSO group and RTX group（ P 0. 05）. Conclusion The subarachnoid injection of TSA can relieve RTX-induced neuropathic pain by up-regulating the expression of brain-derived neurotrophic factor（ BDNF）.