de Geus Thomas J, Franken Glenn, Joosten Elbert A J
Department of Anesthesiology and Pain Management, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Department of Anesthesiology and Pain Management, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Neuromodulation. 2023 Jan;26(1):25-34. doi: 10.1016/j.neurom.2022.04.049. Epub 2022 Aug 2.
Spinal cord stimulation (SCS) is a last-resort treatment for patients with chronic neuropathic pain. The mechanism underlying SCS and pain relief is not yet fully understood. Because the inflammatory balance between pro- and anti-inflammatory molecules in the spinal nociceptive network is pivotal in the development and maintenance of neuropathic pain, the working mechanism of SCS is suggested to be related to the modulation of this balance. The aim of this systematic review is to summarize and understand the effects of different SCS paradigms on the central inflammatory balance in the spinal cord.
A systematic literature search was conducted using MEDLINE, Embase, and PubMed. All articles studying the effects of SCS on inflammatory or glial markers in neuropathic pain models were included. A quality assessment was performed on predetermined entities of bias.
A total of 11 articles were eligible for this systematic review. In general, induction of neuropathic pain in rats results in a proinflammatory state and at the same time an increased activity/expression of microglial and astroglial cells in the spinal cord dorsal horn. Conventional SCS seems to further enhance this proinflammatory state and increase the messenger RNA expression of microglial markers, but it also results in a decrease in microglial protein marker levels. High-frequency and especially differential targeted multiplexed SCS can not only restore the balance between pro- and anti-inflammatory molecules but also minimize the overexpression/activation of glial cells. Quality assessment and risk of bias analysis of the studies included make it clear that the results of these preclinical studies must be interpreted with caution.
In summary, the preclinical findings tend to indicate that there is a distinct SCS paradigm-related effect in the modulation of the central inflammatory balance of the spinal dorsal horn.
脊髓刺激（SCS）是慢性神经性疼痛患者的一种终极治疗手段。SCS及疼痛缓解的潜在机制尚未完全明确。由于脊髓伤害性感受网络中促炎和抗炎分子之间的炎症平衡在神经性疼痛的发生和维持中起关键作用，因此有人提出SCS的作用机制与这种平衡的调节有关。本系统评价的目的是总结并了解不同SCS模式对脊髓中央炎症平衡的影响。
使用MEDLINE、Embase和PubMed进行系统的文献检索。纳入所有研究SCS对神经性疼痛模型中炎症或神经胶质标志物影响的文章。对预先确定的偏倚因素进行质量评估。
共有11篇文章符合本系统评价的要求。一般来说，在大鼠中诱发神经性疼痛会导致促炎状态，同时脊髓背角中小胶质细胞和星形胶质细胞的活性/表达增加。传统的SCS似乎会进一步加剧这种促炎状态，并增加小胶质细胞标志物的信使核糖核酸表达，但它也会导致小胶质细胞蛋白标志物水平下降。高频尤其是差异靶向多重SCS不仅可以恢复促炎和抗炎分子之间的平衡，还可以最大限度地减少神经胶质细胞的过度表达/激活。对纳入研究的质量评估和偏倚风险分析表明，这些临床前研究的结果必须谨慎解读。
总之，临床前研究结果倾向于表明，在调节脊髓背角的中央炎症平衡方面，存在与SCS模式相关的明显效应。
