刺激背外侧前额叶皮层(DLPFC)对骨癌痛的康复作用及机制研究

Cancer pain is a common and stubborn clinical disease, which severely affects the life quality of patients. Recent studies have shown that reorganization of the pain centers in the brain play a very important role in the maintenance of pain. Our previous study indicated that the dorsolateral prefrontal cortex (DLPFC) is closely related to the occurrence of bone cancer pain, and using the transcranial magnetic stimulation (rTMS) to activate the DLPFC could cause exact analgesic effects. According to lately research documents, we hypothesize that: “DLPFC is a specific new therapeutic target for treating bone cancer pain; using some technologies that targeted activation of the DLPFC could enhance the inhibitory effect of the pain centers of the brain, and then cause analgesic effect”. Based on the previous research, we prepare to conduct a clinical RCT study to confirm the therapeutic benefits on patients with bone cancer pain by rTMS. Meanwhile, to further confirm our hypothesis, we prepare to use optogenetics to precisely activate the excitatory neurons of DLPFC. To explore the mechanism of analgesic effect, we will use the functional MRI and neural tract tracing to explore the neural mechanism on bone cancer pain patients and rat model respectively. Based on previous studies, this program firstly regards activation of DLPFC as the.breakthrough point to explore the analgesic effect and mechanism, which may provide new method and theoretical basis for the rehabilitation of cancer pain.

癌痛是临床常见顽疾，严重影响患者的生活质量。最新研究表明大脑痛觉中枢重塑在疼痛的维持中起着关键作用。本课题组研究发现背外侧前额叶皮层（DLPFC）与骨癌痛的发生密切相关，利用重复经颅磁刺激（rTMS）激活DLPFC止痛效果确切。结合相关进展，我们提出如下假说“DLPFC是骨癌痛的特异性治疗靶点，通过相关技术激活DLPFC可以使其对大脑痛觉网络的抑制作用增强，进而发挥镇痛效应”。为了验证上述假说，我们拟通过临床RCT试验证实rTMS技术激活DLPFC治疗骨癌痛的康复疗效；并通过动物实验，利用光遗传学技术精确激活DLPFC的兴奋性神经元，进一步证实上述假说。为了探索机制，我们拟采用fMRI技术、神经环路示踪技术分别对骨癌痛患者及大鼠模型展开镇痛效应的相关机制研究。本项目基于前期发现，首次提出以刺激DLPFC为切入点探讨其对骨癌痛的康复效果及机制，有望为癌痛的康复提供新思路。

癌痛是临床常见顽疾，严重影响患者的生活质量。常用的阿片类药物又存在呕吐、便秘、呼吸抑制等毒副作用，寻找癌痛新型康复治疗方式具有重要的临床意义。研究表明大脑痛觉中枢重塑在疼痛的维持中起着关键作用。本课题组研究发现背外侧前额叶皮层（DLPFC）与骨癌痛的发生密切相关，利用重复经颅磁刺激（rTMS）激活DLPFC止痛效果确切。结合相关进展，我们提出如下假说“DLPFC是骨癌痛的特异性治疗靶点，通过相关技术激活DLPFC可以使其对大脑痛觉网络的抑制作用增强，进而发挥镇痛效应”。为了验证上述假说，我们在本项目资助下，通过临床RCT试验证实了rTMS技术激活DLPFC治疗癌痛的康复疗效；并通过动物实验，利用光遗传学技术精确激活DLPFC的兴奋性神经元，进一步证实了上述假说。目前在该项目资助下，我们通过临床试验证实了经颅磁刺激治疗癌痛的可行性，上述结果已发表SCI论著1篇，中文核心期刊论著1篇、综述1篇，获得专利3项（1项为发明专利，2项为实用新型专利）。相关结果在国际抗癌大会上公布，引起了与会代表的广泛关注。基于本课题组前期临床发现，我们首次提出了在临床上运用 rTMS 技术来缓解骨癌痛，为癌痛患者的治疗提供一种治疗方法。同时，我们利用光遗传学技术对 DLPFC谷氨酸能神经元进行止痛效应研究，研究结果可能为未来开发以DLPFC 谷氨酸能神经元为靶点的新型止痛药物提供了实验依据。