Lind Anne-Li, Emami Khoonsari Payam, Sjödin Marcus, Katila Lenka, Wetterhall Magnus, Gordh Torsten, Kultima Kim
Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, Uppsala, Sweden.
Neuromodulation. 2016 Aug;19(6):549-62. doi: 10.1111/ner.12473.
Electrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action.
Two different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks.
Eighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3).
Previously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain.
脊髓刺激（SCS）进行电神经调节是治疗神经性疼痛的一种成熟方法。然而，患者疼痛缓解效果背后的机制在很大程度上仍不清楚。在本研究中，我们针对人类脑脊液（CSF）蛋白质组，这是SCS作用机制中一个研究较少的方面。
使用两种不同的蛋白质组质谱分析方案，对14名对SCS有反应的神经性疼痛患者的脑脊液进行分析。每位患者自身作为对照，比较刺激器关闭48小时时以及刺激器正常使用三周后的蛋白质含量。
比较刺激器关闭状态和开启状态时，使用SCS的神经性疼痛患者脑脊液中有86种蛋白质发生了统计学上的显著变化。变化最明显的12种蛋白质涉及神经保护（簇集蛋白、凝溶胶蛋白、 mimecan、血管紧张素原、分泌粒蛋白-1、淀粉样β蛋白A4）、突触可塑性/学习/记忆（凝溶胶蛋白、载脂蛋白C1、载脂蛋白E、接触蛋白-1、神经细胞黏附分子L1样蛋白）、伤害性信号传导（神经分泌蛋白VGF）和免疫调节（Dickkopf相关蛋白3）。
证实了SCS对神经保护、伤害性信号传导、免疫调节和突触可塑性相关蛋白质水平有此前未知的影响。在神经性疼痛患者的脑脊液中的这些发现，拓展了SCS对人类脊髓神经化学环境影响的认知。对SCS机制的更好理解可能会带来新的研究方向和改进的神经性疼痛治疗策略。
