Hulata David, Hughes W Frank, Shott Susan, Kroin Jeffrey S, Gonzalez Mark H, Kerns James M
Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States.
J Neurosci Methods. 2008 Jul 30;172(2):236-44. doi: 10.1016/j.jneumeth.2008.05.002. Epub 2008 May 14.
A new partial nerve lesion (PNL) model is needed to better simulate traumatic lesions seen clinically that result in both dysfunction and neuropathic pain. We assessed surgical variability and several outcome measures including histology during the acute postoperative period. A surgical lesion was created in the rat tibial nerve by removing a segment, later confirmed by myelinated axon counts. Variability in the model was assessed with four different outcome measures during the first postoperative week (n=24), with additional histological outcomes at 7 days (n=13) and pain testing at 21 days (n=9). At 7 days postoperative, the PNL resulted in a tibial functional index (TFI) of -41.3% distinct from a percent motor deficit (PMD) of -76.3%. However, the respective deficits from 2 to 7 days were similar. Either test could detect outliers, but PMD measurements had a lower coefficient of variation and were easier to perform and analyze. The deleted segment contained 26% of the myelinated axons and resulted in distal degeneration that was either 46% based on axon counts or 54% based on area. Replicated experiments confirmed the PMD, muscle atrophy, and formation of neuropathic pain. In conclusion, our partial lesion histologically progresses twofold during the first postoperative week with profound behavioral deficits involving both motor and sensory loss. These results based on sensitive and correlative outcome measures support the application of this novel model in experimental nerve lesion studies.
需要一种新的部分神经损伤(PNL)模型,以更好地模拟临床上出现的导致功能障碍和神经性疼痛的创伤性损伤。我们评估了手术变异性以及包括术后急性期组织学在内的几种结果指标。通过切除一段大鼠胫神经来制造手术损伤,随后通过有髓轴突计数进行确认。在术后第一周使用四种不同的结果指标评估模型的变异性(n = 24),在7天时进行额外的组织学结果评估(n = 13),并在21天时进行疼痛测试(n = 9)。术后7天,PNL导致胫神经功能指数(TFI)为 -41.3%,与 -76.3%的运动功能缺损百分比(PMD)不同。然而,从2天到7天各自的缺损情况相似。两种测试都能检测到异常值,但PMD测量的变异系数较低,且更易于执行和分析。切除的节段包含26%的有髓轴突,并导致远端变性,基于轴突计数为46%,基于面积为54%。重复实验证实了PMD、肌肉萎缩和神经性疼痛的形成。总之,我们的部分损伤在术后第一周组织学上进展了两倍,伴有涉及运动和感觉丧失的严重行为缺陷。基于敏感且相关的结果指标的这些结果支持了这种新型模型在实验性神经损伤研究中的应用。