Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
Spine (Phila Pa 1976). 2019 Jan 15;44(2):85-95. doi: 10.1097/BRS.0000000000002776.
Controlled, interventional, animal study.
To investigate the spatial and temporal changes of μ-opioid receptor (MOR) expression in a rat lumbar disc herniation (LDH) model.
MORs widely express in the peripheral and central nervous systems, and opioid drugs produce an analgesic effect through their activation. However, the efficacy of opioid drugs is sometimes inadequate in several pathological conditions of pain. MORs in the brain as well as the spinal cord (SC) and dorsal root ganglion (DRG) are thought to be associated with pain-related behavior, but the underlying mechanisms are not completely understood.
In all, 91 adult female Sprague-Dawley rats were used. Autologous nucleus pulposus (NP) was applied onto the left L5 DRG in the NP group rats. Rats were divided into two surgical groups, the NP and the sham group. The von Frey test of left hind paw was performed before surgery, and 2, 7, 14, 21 and 28 days after surgery. Immunohistochemistry and immunoblotting in the DRG, SC, Caudate putamen, nucleus accumbens (NAc) and periaqueductal grey matter were performed before surgery, and 2, 7, 14, 21 and 28 days after surgery.
The thresholds in the NP group were significantly lower than those in the sham group from day 2 onwards. At days 7 and 14, MOR expression in the injured-side SC and DRG were significantly lower than those in the sham group. At day 21, MOR in the NAc was significantly decreased compared to that in the sham group.
Changes of MOR expression in the NAc, SC and DRG were associated with pain-related behavior. This result might show the underling pathogenesis of the resistance to MOR agonists in the patient with LDH.
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对照、干预、动物研究。
探究大鼠腰椎间盘突出症（LDH）模型中μ 阿片受体（MOR）表达的时空变化。
MOR 在周围和中枢神经系统广泛表达，阿片类药物通过激活 MOR 产生镇痛作用。然而，在几种病理疼痛情况下，阿片类药物的疗效有时并不理想。大脑、脊髓（SC）和背根神经节（DRG）中的 MOR 被认为与疼痛相关行为有关，但潜在机制尚不完全清楚。
共使用 91 只成年雌性 Sprague-Dawley 大鼠。将自体髓核（NP）应用于 NP 组大鼠左侧 L5 DRG。大鼠分为两组手术组，即 NP 组和假手术组。手术前进行左后爪von Frey 测试，术后 2、7、14、21 和 28 天进行测试。手术前和手术后 2、7、14、21 和 28 天对 DRG、SC、尾状核、伏隔核（NAc）和导水管周围灰质进行免疫组织化学和免疫印迹分析。
NP 组大鼠的阈值从第 2 天开始明显低于假手术组。在第 7 天和第 14 天，损伤侧 SC 和 DRG 中的 MOR 表达明显低于假手术组。第 21 天，与假手术组相比，NAc 中的 MOR 显著减少。
NAc、SC 和 DRG 中 MOR 表达的变化与疼痛相关行为有关。这一结果可能表明 LDH 患者对 MOR 激动剂产生耐药性的潜在发病机制。
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