Evaluation of behavior and neuropeptide markers of pain in a simple, sciatic nerve-pinch pain model in rats
Evaluation of behavior and neuropeptide markers of pain in a simple, sciatic nerve-pinch pain model in rats
复制标题
DOI：
10.1007/s00586-010-1428-4
复制
发表时间：
2010-10-01
影响因子：
2.8
通讯作者：
Ohtori, Seiji
中科院分区：
文献类型：
--
作者：
Hirose, Kazutoshi;Iwakura, Nahoko;Ohtori, Seiji
神经损伤疼痛的病理机制尚未完全阐明。建立了根性痛和慢性压迫性损伤模型；然而，制作这些模型很复杂。坐骨神经挤压损伤很容易产生，但该模型用于评估疼痛行为的可靠性尚未得到检验。目前的研究在简单的坐骨神经捏伤模型中评估了大鼠背根神经节（DRG）的疼痛相关行为和疼痛标记物的变化。在模型中，使用镊子夹住坐骨神经 2 秒 (n = 20)，但假手术动物 (n = 20) 并未受伤。使用 von Frey 丝和 Hargreaves 装置每隔一天测量一次机械和热痛觉过敏，持续两周。术后 4 天和 7 天使用免疫组织化学检查 L5 DRG 中降钙素基因相关肽 (CGRP)、激活转录因子 3 (ATF-3)、磷酸化 p38 丝裂原激活蛋白 (Map) 激酶 (p-p38) 和核因子 kappa B (NF-kappa B; p65) 的表达。比较两组之间对这些标记物发生免疫反应的神经元比例。在捏捏组大鼠中发现了机械（8 天）和热痛觉过敏（6 天），但在假手术动物中没有发现（p < 0.05）；然而，第 10 天至第 14 天，痛觉过敏并不显着。与假手术大鼠相比，神经损伤大鼠 L5 DRG 中 CGRP、ATF-3、p-p38 和 NF-kappa B 表达上调（p < 0.01）。我们的结果表明，简单的坐骨神经挤压会产生与疼痛相关的行为。神经损伤模型中疼痛标记物表达的上调表明它可以用作疼痛模型。然而，它被认为不适合长期研究。
Pathomechanisms of injured-nerve pain have not been fully elucidated. Radicular pain and chronic constriction injury models have been established; however, producing these models is complicated. A sciatic nerve-pinch injury is easy to produce but the reliability of this model for evaluating pain behavior has not been examined. The current study evaluated pain-related behavior and change in pain markers in the dorsal root ganglion (DRG) of rats in a simple, sciatic nerve-pinch injury model. In the model, the sciatic nerve was pinched for 2 s using forceps (n = 20), but not injured in sham-operated animals (n = 20). Mechanical and thermal hyperalgesia were measured every second day for 2 weeks using von Frey filaments and a Hargreaves device. Calcitonin gene-related peptide (CGRP), activating transcription factor-3 (ATF-3), phosphorylated p38 mitogen activated protein (Map) kinase (p-p38), and nuclear factor-kappa B (NF-kappa B; p65) expression in L5 DRGs were examined at 4 and 7 days after surgery using immunohistochemistry. The proportion of neurons immunoreactive for these markers was compared between the two groups. Mechanical (during 8 days) and thermal hyperalgesia (during 6 days) were found in the pinch group rats, but not in the sham-operated animals (p < 0.05); however, hyperalgesia was not significant from days 10 to 14. CGRP, ATF-3, p-p38, and NF-kappa B expression in L5 DRGs was upregulated in the nerve-injured rats compared with the sham-operated rats (p < 0.01). Our results indicate that a simple sciatic nerve pinch produced pain-related behavior. Upregulation of the pain-marker expression in the nerve-injury model suggested it could be used as a model of pain. However, it was not considered as suitable for long-term studies.