利用靶向肌肉神经移植干预幻肢痛的效果及机制研究

项目名称： 利用靶向肌肉神经移植干预幻肢痛的效果及机制研究

项目编号： No.81501620

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 吴凤霞

作者单位： 山东大学

项目金额： 18万元

中文摘要： 截肢者不仅能感到截除肢体的存在（幻肢），一些患者还常会感到幻肢疼痛，这给他们身心带来许多痛苦。目前幻肢痛发生机理尚不明确，也缺乏有效的治疗方法。本项目拟利用一种称之为“靶向肌肉神经移植 (TMR)”的新方法及其动物模型，探索TMR对缓解或治疗幻肢痛的效果及干预机制。我们拟用大鼠坐骨神经横断方法建立幻肢痛模型；将坐骨神经近侧断端移植到股二头肌中实现移植神经在靶向肌肉中的分布重建。利用建立的动物模型，拟开展两个方面的研究：①通过动物行为学研究，评价TMR对幻肢痛的治疗效果及最佳手术时机；②利用电镜和膜片钳技术，研究TMR对脊髓和脑皮质S1、M1区内突触形态及功能可塑性的影响； 利用免疫组化、Western blot及免疫沉淀技术，研究PSD-95-NR2B在脊髓和S1、M1区中的表达，了解突触可塑性改变的可能机制。本研究将为研发治疗或缓解幻肢痛的新技术提供理论基础和实验依据。

中文关键词： 靶向肌肉神经移植；幻肢痛；截肢；神经可塑性；PSD；95-NR2B

英文摘要： Phantom limb pain refers to the pain that occurs in a part of the amputated or deafferented limbs. Most of the patients with limb amputations would suffer from phantom limb pain lightly or severely. Currently, the mechanism of phantom limb pain still remains unclear and there have been no efficient treatments for phantom limb pain. In this project, We propose to use a newly developed peripheral nerve reinnervation method called targeted muscle reinnervation (TMR) to treat or relieve phantom limb pain. The therapeutic efectiveness and the possible mechanism of using TMR to relieve phantom limb pain will be investigated by using animals. Phantom limb pain model will be built through transecting sciatic nerves in rats. And then, the proximal ends of these nerves will be transplanted into the biceps femoris(targeted muscle) for reinnervation. Using these animal models, we will conduct the following studies: 1) the treatment effectiveness and the optimal operation timing of TMR on phantom limb pain will be detected via animal ethology; 2)the morphological and functional changes of synapse in spinal cord and primary somatosensory and motor cortex(S1, M1) will be explored by using electron microscopy and the patch clamp; In addition, the expression of PSD-95and NR2B in spinal cord, S1 and M1 will be investiagted by immunohistochemistry staining, Western blot and immunoprecipitation. These studies will help us to understand the mechanism of neural plasticity caused by TMR. The successful implementation of this project will explore the therapeutic potential of TMR in relieving the phantom limb pain and may provide soundly experimental basics for developing a new technique to relieve phantom limb pain for limb amputees.

英文关键词： targeted muscle reinnervation ;phantom limb pain; amputation;neural plasticity;PSD 95-NR2B