Kawakami Mamoru, Hashizume Hiroshi, Matsumoto Takuji, Enyo Yoshio, Okada Motohiro, Yoshida Munehito, Chubinskaya Susan
Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama City, Wakayama, Japan.
Spine (Phila Pa 1976). 2007 Jun 1;32(13):1388-93. doi: 10.1097/BRS.0b013e318060a6b0.
To assess the safety of epidural administration of Osteogenic Protein-1 (OP-1).
To examine if epidural administration of OP-1 or administration into the nucleus pulposus (NP) resulted in ectopic bone formation and/or pain-related behavior.
OP-1 has the potential for treatment of degenerative disc disease. However, OP-1's safety, when it is applied into the epidural space or herniated nucleus pulposus, is not well established.
Forty rats were divided into 5 groups. Sham group: Left L4 and L5 nerve roots were exposed. NP group: The NP obtained from the tail was relocated onto the exposed nerve roots. NP+OP group: The NP obtained from the tail and injected with 0.2 microg of OP-1 in 1 microL of 5% lactose-buffered solution was placed on the nerve roots. GS group: A gelatin sponge was applied on the nerve roots. GS+OP group: A gelatin sponge soaked with 0.2 microg of OP-1 in 1 microL of 5% lactose-buffered solution was placed onto the nerve roots. Motor function and reflex responses to mechanical noxious stimuli were measured in all rats up to 3 weeks after surgery. Three weeks after surgery, all rats were killed for analysis of ectopic bone formation and magnitude of neural compression.
Motor paresis was not observed in any groups. Only rats in the NP group showed evidence of irreversible mechanical hyperalgesia after surgery. There were no differences in the mechanical stimuli response among all groups except the NP group. Macroscopic examination revealed no ectopic bone formation or differences in neural compression among the groups.
OP-1 application in the epidural space is safe based on behavioral measures and macroscopic observation on ectopic bone formation at 21 days after surgery.
评估硬膜外给予成骨蛋白-1（OP-1）的安全性。
研究硬膜外给予OP-1或注入髓核（NP）是否会导致异位骨形成和/或疼痛相关行为。
OP-1具有治疗椎间盘退变疾病的潜力。然而，将OP-1应用于硬膜外间隙或突出的髓核时，其安全性尚未明确。
40只大鼠分为5组。假手术组：暴露左侧L4和L5神经根。NP组：将取自尾部的髓核重新置于暴露的神经根上。NP + OP组：将取自尾部并在1微升5%乳糖缓冲溶液中注入0.2微克OP-1的髓核置于神经根上。GS组：在神经根上放置明胶海绵。GS + OP组：将在1微升5%乳糖缓冲溶液中浸泡有0.2微克OP-1的明胶海绵置于神经根上。在术后长达3周的时间内测量所有大鼠的运动功能以及对机械性有害刺激的反射反应。术后3周，处死所有大鼠以分析异位骨形成情况和神经受压程度。
所有组均未观察到运动麻痹。仅NP组大鼠术后出现不可逆的机械性痛觉过敏。除NP组外，所有组在机械刺激反应方面无差异。宏观检查显示各组之间均未出现异位骨形成或神经受压差异。
基于行为学测量以及术后21天对异位骨形成的宏观观察，硬膜外应用OP-1是安全的。
