Harrington J F, Messier A A, Bereiter D, Barnes B, Epstein M H
Brown University School of Medicine and the Rhode Island Hospital, Providence, Rhode Island, USA.
Spine (Phila Pa 1976). 2000 Apr 15;25(8):929-36. doi: 10.1097/00007632-200004150-00006.
Combined prospective human cohort and prospective controlled animal model.
To determine whether free glutamate is available in herniated disc material in concentrations sufficient to diffuse to glutamate receptors and affect the activity of neurons in the dorsal root ganglion that may transmit pain information.
The severity of lumbar radicular pain cannot be fully explained by physical pressure on nerve roots or ganglions. In experimental models, inflammatory processes are relatively modest under conditions of disc herniation. The hypothesis for the current study was that the proteoglycan link and core proteins, which contain high fractions of acidic amino acids, may be a source of glutamate when enzymatically degraded in an environment without glutamate reuptake systems. Glutamate would be free to diffuse to the dorsal root ganglion to affect glutamate receptors.
Disc material was harvested during surgery from herniated and nonherniated portions in patients undergoing elective lumbar disc surgery and subjected to immunohistochemistry and high-performance liquid chromatography for assessment of the presence of extracellular disc matrix glutamate. Miniosmotic pumps with differing concentrations of radiolabeled glutamate based on human data were implanted in the rat epidural space for 72 hours and dorsal root ganglion (DRG) in the region were harvested.
Densitometry of disc matrix demonstrated immunohistochemical evidence for significant extracellular glutamate (P < 0.002). High performance liquid chromatography showed significant concentrations of glutamate in disc material and significantly more in herniated than in nonherniated disc material (P < 0.05). Significant radiolabeling of the dorsal root ganglion after epidural glutamate infusion was found at concentrations two orders of magnitude below measured disc glutamate levels. Autoradiography demonstrated radiolabeling of adjacent DRG.
Glutamate originating from degenerated disc proteoglycan may diffuse to the dorsal root ganglion and effect glutamate receptors. Consideration may be given to treating disc radiculopathy with epidural glutamate receptor antagonists.
前瞻性人体队列与前瞻性对照动物模型相结合。
确定游离谷氨酸在椎间盘突出物中的浓度是否足以扩散至谷氨酸受体并影响可能传递疼痛信息的背根神经节中神经元的活性。
腰椎神经根性疼痛的严重程度不能完全由神经根或神经节上的物理压力来解释。在实验模型中，椎间盘突出情况下的炎症过程相对较轻。本研究的假设是，含有高比例酸性氨基酸的蛋白聚糖连接物和核心蛋白，在没有谷氨酸再摄取系统的环境中被酶降解时，可能是谷氨酸的来源。谷氨酸可自由扩散至背根神经节以影响谷氨酸受体。
在择期腰椎间盘手术患者中，于手术期间从椎间盘突出和未突出部分采集椎间盘组织，进行免疫组织化学和高效液相色谱分析，以评估细胞外椎间盘基质中谷氨酸的存在情况。根据人体数据，将不同浓度放射性标记谷氨酸的微型渗透泵植入大鼠硬膜外间隙72小时，然后采集该区域的背根神经节。
椎间盘基质的光密度测定显示，免疫组织化学证据表明存在大量细胞外谷氨酸（P < 0.002）。高效液相色谱显示，椎间盘组织中谷氨酸浓度显著，且突出椎间盘组织中的谷氨酸浓度显著高于未突出椎间盘组织（P < 0.05）。硬膜外注入谷氨酸后，在浓度比测得的椎间盘谷氨酸水平低两个数量级时，发现背根神经节有显著的放射性标记。放射自显影显示相邻背根神经节有放射性标记。
源自退变椎间盘蛋白聚糖的谷氨酸可能扩散至背根神经节并影响谷氨酸受体。可考虑用硬膜外谷氨酸受体拮抗剂治疗椎间盘神经根病。
