外周信号通路改变“打破大脑疼痛环路”治疗灼性神经痛的中枢网络机制研究

Sever peripheral nerve injury, such as brachial plexus injury, may lead to intractable causalgia. The disease has a high incidence and difficult to treat in clinics, which makes the patients miserable. It also brings heavy burden to the society and family. The latest clinical investigation trying to suppress the pain through peripheral nerve transfer. However, its central mechanism is not clear. Related investigations indicated that chronic pain could activate the “pain loop” in the patients’ brain, and then the “pain memory”, which is a hard problem to deal with. We assumed that the alteration of peripheral pathway could induce the cortical remodeling, which broke the brain “pain loop” and produced significant analgesic effect for a long time. This project attempts to fulfill this hypothesis by using the neuroimaging and in vivo electrophysiological techniques to explore the central dynamic remodeling mechanisms of peripheral nerve transfer treating causalgia. Neuro- electrical stimulation is also used for regulating the peripheral afferent signals, to promote brain plasticity, furthermore, enhance the analgesic effect. This project could provide new ideas for clinical choice to solve the difficult of treating causalgia.

严重的周围神经损伤如臂丛损伤后，会发生难治性灼性神经痛，其发病率高、治疗困难，令患者痛苦不堪，也给社会和家庭带来了沉重的负担。临床最新尝试通过周围神经移位、改变外周信号传入通路的方法来治疗疼痛并获得好的长期疗效，但是其内在的中枢的机制尚不明确。相关研究表明，长期处于慢性疼痛状态易激活患者的大脑“疼痛环路”，进而形成“疼痛记忆”，而这一记忆和疼痛相互作用会使患者的疼痛更加难以治疗和缓解。我们认为周围神经通路的改变可以影响大脑的感觉信号传入，诱发重塑，进而打破“疼痛环路”，产生长期显著的镇痛效果。本项目拟针对这一假说，综合采用神经功能影像学和在体神经电生理学的研究方法，在宏观和微观层面探索周围神经移位治疗灼性神经痛的中枢动态重塑模式，并尝试结合神经电刺激进行信号传入的调控，促进大脑的有利重塑，进一步增强其镇痛疗效，为临床解决灼性神经痛这一难题提供新的思路和选择。

严重的周围神经损伤如臂丛损伤后，会发生难治性灼性神经痛，其发病率高、治疗困难，令患者痛苦不堪，也给社会和家庭带来了沉重的负担。本项目基于最新的远端周围神经移位技术、改变外周信号传入通路的方法来治疗疼痛，综合运用电生理和功能影像学的方法，发现外周信号的改变可以以影响大脑的感觉信号传入，诱发重塑，进而打破“疼痛环路”改变治疗臂丛损伤后灼性神经痛的中枢动态重塑模式，改善慢性疼痛的临床症状。其中功能影像学和研究发现，电生理感觉-运动网络、疼痛相关的脑区网络、边缘系统脑区均发生了脑区-连接-网络层面的重塑，激活了中枢镇痛环路，抑制了疼痛环路，进而改变了慢性神经病理性疼痛不断自我强化的疼痛记忆和疼痛知觉系统。同时本项目将周围神经移位手术治疗和神经电刺激进行信号传入的调控，促进大脑的有利重塑，进一步增强其镇痛疗效，为临床解决灼性神经痛这一难题提供新的思路和选择。