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交感神经芽生对神经病理性疼痛大鼠的影响及其机制

发布时间:2018-11-14 18:14
【摘要】:目的:为了研究交感神经系统对神经病理性疼痛的调控机理。我们在大鼠的慢性压迫背根神经节(chronic compression of dorsal root ganglion,CCD)模型上给予交感神经阻断剂胍乙啶(Guanethidine,GU)后,观察实验大鼠背根神经节(dorsal root ganglion,DRG)内交感神经芽生的分布状况,以及后者对实验大鼠疼痛行为学的影响,并探讨交感神经芽生对神经病理性疼痛的作用及其机制。方法:1、将雄性SD大鼠随机分为Sham组和CCD组,采用von Frey纤维丝监测其50%机械性刺激缩足反射阈值的改变;并且于造模后第28天取各组实验大鼠背根神经节,甲醛固定后,做冰冻切片,采用免疫荧光染色技术研究大鼠背根神经节内交感神经芽生的分布变化趋势,分析其与疼痛行为之间的关系。2、将雄性SD大鼠随机分为Sham组、CCD+NS组、CCD+Guanethidine组,采用von Frey纤维丝观察各组大鼠的50%机械性刺激缩足反射阈值的改变,研究术前经腹腔途径注射交感神经阻断剂胍乙啶对慢性压迫背根神经节模型大鼠机械性刺激痛觉过敏行为的影响,并且于造模后第28天取各组实验大鼠背根神经节,经过甲醛固定后,做冰冻切片,再应用免疫荧光染色技术研究试验大鼠背根神经节内交感神经芽生分布的变化趋势,分析其与实验大鼠机械性刺激疼痛行为之间的关系,探讨胍乙啶对疼痛和炎性反应的影响。结果:1、建立慢性压迫背根神经节模型后,实验大鼠双侧后肢50%机械性刺激缩足反射阈值与Sham组实验大鼠相比较明显下降(P0.01)。在交感神经芽生分布这一方面,慢性压迫背根神经节造模术后第28天交感神经芽生的分布明显增多(P0.01),且明显高于Sham组,具有统计学意义。2、经腹腔注射交感神经阻断剂胍乙啶可明显提高背根神经节慢性压迫模型大鼠的机械性刺激缩足阈值,与CCD+NS组相比,具有明显差异;而经腹腔注射生理盐水对正常大鼠的50%机械性刺激缩足反射阈值并无明显影响。免疫荧光染色实验结果显示,胍乙啶可使慢性压迫背根神经节模型大鼠背根神经节上的交感神经芽生分布明显减少,与CCD+NS组实验大鼠相比,具有明显的统计学差异。结论:1、交感神经芽生在受慢性压迫的背根神经节上的分布明显增多,而且慢性持续性压迫背根神经节能显著降低大鼠的机械性刺激痛阈,提示背根神经节内的交感神经芽生可能参与了大鼠神经病理性疼痛的形成和维持。2、交感神经阻断剂胍乙啶可明显抑制由慢性压迫背根神经节模型引起的大鼠神经病理性疼痛,同时也减少了受慢性压迫的背根神经节上交感神经芽生的分布,进一步说明大鼠背根神经节内出现的交感神经芽生与神经病理性疼痛形成和维持可能存在关联。
[Abstract]:Objective: to study the regulation mechanism of sympathetic nervous system on neuropathic pain. We treated the rat model of chronic compression of dorsal root ganglion (chronic compression of dorsal root ganglion,CCD) with aganidine (Guanethidine,GU), a sympathetic nerve blocker, and observed (dorsal root ganglion, in the experimental rat dorsal root ganglion (DRG). The distribution of sympathetic nerve buds in DRG and the effect of the latter on the pain behavior of experimental rats were also discussed. The effects of sympathetic nerve buds on neuropathic pain and its mechanism were also discussed. Methods: 1. Male SD rats were randomly divided into Sham group and CCD group. The changes of reflex threshold of 50% mechanical stimulation were monitored by von Frey filament. On the 28th day after the model, the experimental rats' dorsal root ganglia were taken and fixed with formaldehyde, then frozen sections were made. The distribution of sympathetic nerve buds in the dorsal root ganglion of rats was studied by immunofluorescence staining. 2the male SD rats were randomly divided into Sham group (, CCD NS group) and, CCD Guanethidine group (, CCD NS group). The changes of reflex threshold of 50% mechanical stimulation in each group were observed with von Frey filament. To study the effect of intraperitoneal injection of guanidine, a sympathetic nerve blocker, on hyperalgesia in rats with chronic compression of dorsal root ganglion (DRG). After formalin fixation, frozen sections were made, and then the distribution of sympathetic nerve buds in dorsal root ganglion of experimental rats was studied by immunofluorescence staining, and the relationship between the distribution of sympathetic nerve buds and the pain behavior of mechanical stimulation in experimental rats was analyzed. To investigate the effect of guanidine on pain and inflammatory response. Results: 1. After establishing the model of chronic compression of dorsal root ganglion, the reflex threshold of 50% mechanical stimulation on both hind limbs of experimental rats was significantly lower than that of experimental rats in Sham group (P0.01). In the distribution of sympathetic nerve buds, the distribution of sympathetic nerve buds increased significantly on the 28th day after chronic compression of dorsal root ganglion model (P0.01), and was significantly higher than that in Sham group, which was statistically significant. Intravenous injection of guanidine, a sympathetic nerve blocker, significantly increased the threshold of mechanical stimulation in rats with chronic compression of dorsal root ganglion (DRG), which was significantly different from that in CCD NS group. However, intraperitoneal injection of normal saline had no significant effect on the reflex threshold of 50% mechanical stimulation in normal rats. The results of immunofluorescence staining showed that guanidine could significantly reduce the distribution of sympathetic nerve buds in the dorsal root ganglion of rats with chronic compression of dorsal root ganglion (DRG), which was significantly different from that of the experimental rats in CCD NS group. Conclusion: 1. The distribution of sympathetic nerve buds on the dorsal root ganglion (DRG) under chronic compression was significantly increased, and the energy saving of chronic continuous compression of DRN significantly decreased the pain threshold of mechanical stimulation in rats. These results suggest that sympathetic nerve sprouting in dorsal root ganglion may be involved in the formation and maintenance of neuropathic pain in rats. The sympathetic blocker guanidine inhibited the neuropathic pain induced by chronic compression of the dorsal root ganglion in rats, and also reduced the distribution of sympathetic nerve buds on the dorsal root ganglion under chronic compression. It is further suggested that the sympathetic ganglia in the dorsal root ganglion of rats may be associated with the formation and maintenance of neuropathic pain.
【学位授予单位】:广东药科大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R402

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