大鼠分级坐骨神经缩窄致神经病理性疼痛模型的行为学及病理学评估

BEHAVIORAL AND PATHOLOGIC ASSESSMENT OF GRADED NEUROPATHIC PAIN DEVELOPED BY GRADED SCIATIC CONSTRICTION IN RAT MODEL

目的:建立不同程度的大鼠神经病理性疼痛模型,评价其行为学和病理学变化的关系。方法:30只雄性SD大鼠随机均分为C,N0,N1,N2,N4组(n=6),用分级坐骨神经缩窄法建立动物模型。在术前和术后3、7、10、14天测定大鼠右后爪50%缩爪阈值。术后第15天取右侧坐骨神经横断面切片行Luxol fast blue染色,计算坐骨神经环扎远端髓鞘计数占近端髓鞘计数百分比(the ratiosof the myelin sheath counts in the distal sections to those in the proximal sections of the sciatic nerve,DPR)。用SPSS 13.0进行数据分析。结果:大鼠右后爪50%缩爪阈值在C组和N0组无明显改变,在N1、N2和N4组大鼠术后较术前明显下降,至术后14天N0>N1>N2>N4(P<0.05)。C组和N0组大鼠右侧坐骨神经无明显病理学改变,N1、N2和N4组环扎远端神经纤维出现不同程度的脱髓鞘改变。术后14天大鼠50%缩爪阈值与其DPR值间Spearman相关系数rp=0.901(P<0.001)。结论:大鼠分级坐骨神经缩窄模型可导致手术侧坐骨神经不同程度的脱髓鞘病变,引起不同程度的神经病理性疼痛,其病理学变化与行为学有显著相关性。

Objective： To develop a rat model of graded neuropathic pain by graded sciatic constriction and to assess the behavioral and pathologic changes of the model. Methods： 30 male SD rats were randomly allocated equally in 5 groups （group No, N1, N2, N4 and C, n = 6 for each group） and received graded right sciatic constriction. Mechanical allodynia was assessed with von Frey hairs before operation and on the 3rd, 7th, 10th and 14th postoperative days, and the 50% withdraw threshold was calculated with up-and- down method. On the 15th postoperative day, the rats were sacrificed and the right sciatic nerve were dissected for transverse slicing and myelin staining with Luxol fast blue. Counts of the myelin sheaths in the proximal or distal areas of the sciatic nerve were performed under 400 magnifications, and the ratios of the myelin sheath counts in the distal areas to those in the proximal areas （DPR） were calculated. Statistical analysis was performed with SPSS 13.0. Results： The 50% withdraw threshold of the right foot dropped dramatically in group N1, N2 and N4 from the 3rd day and maintained at the lowest level from the 7-10th day to 2 weeks postoperatively （P 〈 0.001 compared to group No and C）. On the 14th day, the 50% withdraw threshold presented a graded manifestation of No 〉 N1 〉 N2 〉 N4 （P 〈 0.05）. Graded demyelination （NO 〈 N1, N2 〈 N4, P 〈 0.001） was also observed in the distal area of the ligated sciatic nerve, represented digitally by the myelin sheath counts and the DPR value. The Pearson correlation coefficients between DPR value and the 50% withdraw threshold on the 14th day was 0.860. Conclusion： The graded model of neuropathic pain can be developed by graded constriction of the sciatic nerve with a pathologic basis of different degrees of demyelination. The behavioral manifestation is correlated with the pathologic changes.