大鼠自体神经移植与外周神经挤压再生模型脊髓背角c-fos表达的比较研究

目的建立大鼠外周神经挤压神经再生模型和大鼠外周神经自体神经移植神经再生模型,观察对比各模型神经恢复过程中机械痛觉超敏的变化及脊髓背角c-fos表达的改变,探讨两种神经再生模型中神经再生与神经性疼痛的联系。方法雄性Wistar大鼠60只随机均分成3组,A组为坐骨神经挤压模型组;B组为自体神经移植模型组;C组为假手术组。分别制成模型后,术后18d起检测机械刺激阈值及c-fos表达计数。结果A、B组各项指标与C组比较有显著差异;A组各指标与B组有显著差异。结论两种模型再生神经生长进入去神经支配区域时,均出现支配区域的痛觉超敏和疼痛相关行为,神经性疼痛的发生时间、强度以及恢复均有不同,并和神经再生情况相关,提示神经性疼痛是评估神经功能恢复的一个重要的参数。

Comparative Study of Rat Arterial Autograft Model and Scarve Nerve Crucn Model with Mechanic Withdrawal Threshold And c-fos Expression in the Superficial Dorsal Horn

Objective The purpose of this study was to investigate whether two nerve injury in rats alters the behavioral response to tactile stimuli and whether this is associated with a change in the pattern of c-fos expression in the dorsal horn.Methods 60 male wistar rats were randomly divided into foue groups: sciatic nerve injury (group A,n=20) autograft (group B,n=20) sham-operation (group C,n=20) and. Food and water were available adlibitum, and the rats were kept in a colony room with an ambient temperature of 22°C, and a 12-hour alternating light-dark cycle. The rats in A group underwent a sciatic nerve crush. Under Fluothane anesthesia the right sciatic nerve was crushed with a smoothed-tipped forceps for 30 seconds, until translucent. The rats in B group underwent right sciatic nerve trancection and keep a 10mm nerve defect,and then repaired autograft.The right sciatic nerve was exposed but not crushed under the standard anaesthetic regimen in C group. The wound was sutured in all animals.The peocess of regeneration of peripheral nerve and neuropathic pain were evaluated at 18 to 39 days following opration Mechanic withdrawal threshold and thermal withdrawal latensy were assessed by von-fray filaments 18,21,24,27,30,33,36,39 d after opration. Five rats of each group were given innoxious touch-stimulus for 2 hours before killed 21,27,33,39d after opration. The spinal cord was obtained after death. Immunohistochemistry was employed to investigate the expression of the c-fos.Results The hyperalgesia appeared on the 18th day after injury-operation of the sciatic nerve and reached its maximal level on the 21th day after operation in A group. At 39th day, the threshold of A group was still significantly different as compared to the C group animals. The hyperalgesia of B group appeared on the 24th day after injury-operation of the sciatic nerve and reached its maximal level on the 27th day after operation. On paralleled with hyperalgesia , the expression of c-fos elicited by touch-stimulus increased significantly and it mainly distributed at middle of superficial layer in laminal Ⅰ-Ⅱ in spinal dorsal horn in A and B groups by touch-stimulus. The expression of c-fos significantly decrease between 21th and 39th day in A group. The expression of c-fos significantly decrease between 27th and 39th day in B group. And there had a significant difference in c-fos expression between A and B groups. Conclusion After sciatic nerve crush lesions, however, once the injured fibers have regrown into the denervated skin, touch stimuli both produce pain-related behavior and induce c-fos expression in these normally nociceptive specific regions. We conclude that after nerve injury, low threshold mechanoreceptor fibers may play a major role in producing pain-related behavior by activating normally nociceptive-specific regions of the central nervous system such as the superficial laminae of the dorsal horn.