眶下孔周围注射滑石粉制作新型大鼠三叉神经痛动物模型的实验研究

目的: 应用滑石粉悬液进行眶下孔周围注射,建立一种新型大鼠三叉神经痛（trigeminal neuralgia,TN）动物模型。方法: 选取Wistar雄性大鼠30只,随机分为2组,一组在眶下神经孔周围注射30%滑石粉混悬液0.3 mL,另一组注射同等剂量的生理盐水,于术前3 d、术后3 d及术后1、2、3、4、6、8、12周分别进行行为学观察,Von Frey纤维测定大鼠机械性刺激反应阈值,利用方差分析对机械刺激阈值进行统计学分析。于术后3 d及术后4、8、12周取眶下孔周围组织作组织病理学观察,应用免疫组织化学的方法检测眶下区组织肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)的表达,采用SPSS16.0软件包对各检测值进行分组t检验。结果: 实验组大鼠术后3 d眶下神经支配区域机械痛反应阈值与术前及对照组相比显著降低（P<0.01),大鼠易激惹,具有搔抓面部或攻击行为。直到术后12周,机械痛阈值仍然显著低于对照组。实验组术后3 d组织病理学观察主要呈炎症表现,炎性因子表达减少;术后1周炎症更剧烈,炎性因子表达。术后4周,局部出现炎性肉芽组织增生,炎性因子表达最高;4~12周炎性反应逐渐减轻,炎性因子表达逐渐减少,局部瘢痕形成并逐渐加重,可见瘢痕压迫眶下神经。结论: 眶下孔周围注射滑石粉悬液可以建立稳定的TN动物模型,该造模方法简单易行,为进一步研究TN发病机制和模拟临床治疗提供了一种可靠、有效的动物模型。

Experimental study of a new animal model with trigeminal neuralgia produced by administration of talc to peripheral infraobital nerve in rats

PURPOSE: To establish a new animal model of trigeminal neuralgia（TN） produced by administration of talc to peripheral infraobital nerve in rats. METHODS: Thirty male Wistar rats were randomly divided into 2 groups. Talcum powder (30%,0.3 mL) was injected into the peripheral infraorbital foramen in one group, the same dose of normal saline was injected by the same method in another group. On 3 day before surgery and 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 and 12 weeks postoperatively, mechanical pain behavior was determined. Statistical analysis of the threshold of pain response was performed and the behavior of pain was observed in the area of infraorbital nerve innervation in rats. Histopathological changes of the peripheral infraorbital nerve tissue in the rats were observed 3 days, 4 weeks, 8 weeks and 12 weeks postoperatively. The expression of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin -1β (IL-1β) in the territory of the infraorbital nerve was detected by immunohistochemistry. SPSS16.0 software package was used to analyze the data. RESULTS: The mechanical pain threshold of rats in the infraorbital innervation area 3 days postoperatively in the experimental group was significantly decreased compared with that in the preoperative group and the control group (P<0.01). The rats in the experimental group 3 days postoperatively experienced symptoms of irritability, scratching the face or aggressive behavior. Twelve weeks after operation, the mechanical pain threshold was still significantly decreased. Histopathological examination in the experimental group 3 days postoperatively mainly showed inflammation with a few inflammatory factors（IL-1β and TNF-α）expression. Inflammation in the experimental group 1week postoperatively was more intense and more inflammatory factors were expressed. Four weeks postoperatively, there was more proliferation of granulation tissue in the area of peripheral infraorbital nerve tissue and expression of inflammatory factors was highest. Four to twelve weeks, the inflammatory response in the experimental group was gradually reduced, increased scar and infraorbital nerve compressing by scar were observed, and the expression of inflammatory factors decreased gradually. CONCLUSIONS: Injection of talc to the peripheral infraorbital foramen can establish a reliable and stable animal model for research of etiology and treatment of TN.