本研究检查了P2X7受体敲除(KO)如何调节由丘脑腹基底复合体(VBC)病变引起的中枢中风后疼痛(CPSP)的行为,分子水平,和电气记录测试。按照实验程序,野生型和P2X7受体KO小鼠在丘脑的VBC中注射10mU/0.2μLIV型胶原酶,以诱导中风样丘脑出血的动物模型.行为数据显示CPSP组可引起热痛和机械性疼痛。与CPSP组相比,P2X7受体KO组显示出降低的热和机械疼痛反应。分子评估显示,CPSP组NeuN和KCC2的表达较低,GFAP的表达较高。IBA1和BDNF。P2X7KO组GFAP表达较低,IBA1和BDNF但KCC2表达与CPSP组相比无显著差异。NKCC1、GABAa受体的表达,和TrkB在对照组之间没有显着差异,CPSP,和P2X7受体KO基团。Muscimol,一种GABAa激动剂,应用增加了多单位数,用于监测CPSP组中细胞溶胶中的许多神经元和[Cl-]流出,与CPSP组相比,P2X7受体KO降低了多单位活性并增加了[Cl-]内流。在P2X7受体KO组中,P2X4受体表达在100kDa位点中显著降低,但在50kDa位点中没有显著降低。总之,提出了CPSP的P2X7假设,其中P2X7受体KO改变了CPSP疼痛反应,星形胶质细胞和小胶质细胞的数量,前扣带回皮质和内侧背侧丘脑的CSD振幅,BDNF表达,[Cl-]涌入,和P2X4在100kDa中与P2X7受体表达。本发现对CPSP症状的临床治疗具有重要意义。
The present study examined how P2X7 receptor knockout (KO) modulates central post-stroke pain (CPSP) induced by lesions of the ventrobasal complex (VBC) of the thalamus in behaviors, molecular levels, and electrical recording tests. Following the experimental procedure, the wild-type and P2X7 receptor KO mice were injected with 10 mU/0.2 μL type IV collagenase in the VBC of the thalamus to induce an animal model of stroke-like thalamic hemorrhage. Behavioral data showed that the CPSP group induced thermal and mechanical pain. The P2X7 receptor KO group showed reduced thermal and mechanical pain responses compared to the CPSP group. Molecular assessments revealed that the CPSP group had lower expression of NeuN and KCC2 and higher expression of GFAP, IBA1, and BDNF. The P2X7 KO group showed lower expression of GFAP, IBA1, and BDNF but nonsignificant differences in KCC2 expression than the CPSP group. The expression of NKCC1, GABAa receptor, and TrkB did not differ significantly between the control, CPSP, and P2X7 receptor KO groups.
Muscimol, a GABAa agonist, application increased multiunit numbers for monitoring many neurons and [Cl-] outflux in the cytosol in the CPSP group, while P2X7 receptor KO reduced multiunit activity and increased [Cl-] influx compared to the CPSP group. P2X4 receptor expression was significantly decreased in the 100 kDa but not the 50 kDa site in the P2X7 receptor KO group. Altogether, the P2X7 hypothesis of CPSP was proposed, wherein P2X7 receptor KO altered the CPSP pain responses, numbers of astrocytes and microglia, CSD amplitude of the anterior cingulate cortex and the medial dorsal thalamus, BDNF expression, [Cl-] influx, and P2X4 expression in 100 kDa with P2X7 receptors. The present findings have implications for the clinical treatment of CPSP symptoms.