Zhao Qing, Zhao Lijuan, Fan Pianpian, Zhu Yanjing, Zhu Rongrong, Cheng Liming, Xie Ning
Division of Spine, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, 200065, China.
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, 200065, China.
Heliyon. 2024 Aug 10;10(16):e36061. doi: 10.1016/j.heliyon.2024.e36061. eCollection 2024 Aug 30.
Patients with spinal cord injury (SCI) often suffer from varying degrees of neuropathic pain. Non-invasive repetitive transcranial magnetic stimulation (TMS) has been shown to improve neuropathic pain, while the appropriate intervention strategies of TMS treatment and how TMS affects brain function after SCI were not entirely clear. To investigate the effects and mechanisms of TMS on neuropathic pain after SCI, high-frequency TMS on primary motor cortex (M1) of mice was performed after SCI and pain response was evaluated through an electronic Von-Frey device and cold/hot plates. Functional magnetic resonance imaging (fMRI), bulk RNA sequencing, immunofluorescence and molecular experiments were used to evaluate brain and spinal cord function changes and mechanisms. TMS significantly improved SCI induced mechanical allodynia, cold and thermal hyperalgesia with a durative effect, and TMS intervention at 1 week after SCI had pain relief advantages than at 2 weeks. TMS intervention not only affected the functional connections between the primary motor cortex and the thalamus, but also increased the close connection of multiple brain regions. Importantly, TMS treatment activated the hypothalamic pituitary adrenal (HPA) axis and increased the transcript levels of genes encode hormone proteins, accompanied with the attenuation of inflammatory microenvironment in spinal cord associated with pain relief. Totally, these results elucidate that early intervention with TMS could improve neuropathic pain after SCI associated with enhancing brain functional connectivity and HPA axis activity which should be harnessed to modulate neuropathic pain after SCI.
脊髓损伤（SCI）患者常遭受不同程度的神经性疼痛。无创重复经颅磁刺激（TMS）已被证明可改善神经性疼痛，而TMS治疗的适当干预策略以及SCI后TMS如何影响脑功能尚不完全清楚。为了研究TMS对SCI后神经性疼痛的影响及机制，在SCI后对小鼠初级运动皮层（M1）进行高频TMS，并通过电子von Frey装置和冷/热板评估疼痛反应。采用功能磁共振成像（fMRI）、批量RNA测序、免疫荧光和分子实验来评估脑和脊髓功能变化及机制。TMS显著改善了SCI诱导的机械性异常性疼痛、冷觉和热觉过敏，并具有持续效应，且SCI后1周进行TMS干预比2周时具有更好的疼痛缓解优势。TMS干预不仅影响初级运动皮层与丘脑之间的功能连接，还增加了多个脑区的紧密连接。重要的是，TMS治疗激活了下丘脑-垂体-肾上腺（HPA）轴，增加了编码激素蛋白的基因转录水平，同时伴随着与疼痛缓解相关的脊髓炎症微环境的减轻。总之，这些结果表明，早期进行TMS干预可改善SCI后的神经性疼痛，这与增强脑功能连接性和HPA轴活性有关，可利用这一点来调节SCI后的神经性疼痛。
