Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Orthopaedic Surgery, Maruyama Orthopaedic Hospital, Sapporo, Japan.
Spine (Phila Pa 1976). 2018 Mar 15;43(6):E321-E326. doi: 10.1097/BRS.0000000000002333.
Animal experimental study with intervention.
The purpose of this study was to elucidate whether local administration of an α-antagonist around the dorsal root ganglion (DRG) suppressed sympathetic nerve sprouting, from the acute to the chronic pain development phase, in a lumbar radiculopathy model using immunohistochemical methods.
The abnormal sympathetic-somatosensory interaction may underlie some forms of neuropathic pain. There were several reports suggesting α-antagonists are effective to treat neuropathic pain. However, its pathophysiological mechanisms remain obscure.
We used 70 male Sprague-Dawley rats. After root constriction (RC), rats received a series of three local injections of the nonselective α-antagonist phentolamine around the DRG for 3 days. There were three groups of rats: those that were injected from the day of surgery and those injected from day 4 and third group injected from day 11. The control rats were subjected to RC but equal-volume normal saline injections, and the naïve rats were not subjected to any surgical procedures. At the 14th postoperative day, the left L5 DRG was removed, embedded in paraffin, and sectioned. Sections were then immunostained with antibodies to tyrosine hydroxylase (TH). To quantify the extent of the presence of sympathetic nerve fibers, we counted TH-immunoreactive fibers in the DRG using a light microscope equipped with a micrometer graticule. We counted the squares of the graticule, which contained TH-immunoreactive fibers for each of five randomly selected sections of the DRG.
In the naïve group, TH-immunoreactive fibers were scarce in the DRG. α-antagonist injections from postoperative day 0 and 4 suppressed sympathetic nerve sprouting compared with the control group. α-antagonist injections from postoperative day 11 had no suppressant effect compared with the control group.
The α-antagonist administered around the DRG could suppress neural plastic changes in the early phase after nerve injury.
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动物实验研究,干预措施为局部给药。
本研究旨在通过免疫组织化学方法阐明在腰椎神经根病模型中,局部给予背根神经节(DRG)周围的α-拮抗剂是否可以抑制从急性到慢性疼痛发展阶段的交感神经发芽。
异常的交感神经-感觉神经相互作用可能是某些形式的神经病理性疼痛的基础。有几项报告表明,α-拮抗剂对治疗神经病理性疼痛有效。然而,其病理生理学机制尚不清楚。
我们使用了 70 只雄性 Sprague-Dawley 大鼠。在神经根受压(RC)后,大鼠连续 3 天接受 DRG 周围非选择性α-拮抗剂酚妥拉明的一系列 3 次局部注射。有三组大鼠:手术当天开始注射的大鼠、术后第 4 天开始注射的大鼠和第 11 天开始注射的大鼠。对照组大鼠仅接受 RC 和等容量生理盐水注射,而未接受任何手术的大鼠为空白对照。术后第 14 天,取出左侧 L5 DRG,包埋在石蜡中并切片。然后用酪氨酸羟化酶(TH)抗体对切片进行免疫染色。为了量化交感神经纤维存在的程度,我们使用配备有测微计网格的显微镜对 DRG 中的 TH-免疫反应性纤维进行计数。我们对 DRG 中 5 个随机选择的切片的每个测微计网格方格中包含 TH-免疫反应性纤维的方格进行计数。
在空白对照组中,DRG 中 TH-免疫反应性纤维稀少。与对照组相比,术后第 0 天和第 4 天开始注射α-拮抗剂可抑制交感神经发芽。与对照组相比,术后第 11 天开始注射α-拮抗剂无抑制作用。
DRG 周围给予的α-拮抗剂可以抑制神经损伤后早期的神经可塑性变化。
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