Kriek Nadia, Schreurs Marco W J, Groeneweg J George, Dik Wim A, Tjiang Gilbert C H, Gültuna Ismail, Stronks Dirk L, Huygen Frank J P M
Center for Pain Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Neuromodulation. 2018 Jan;21(1):77-86. doi: 10.1111/ner.12704. Epub 2017 Oct 24.
Complex regional pain syndrome (CRPS) is characterized by continued pain disproportional to the inciting event, sensory abnormalities, vasomotor and sudomotor disturbances, and motor and trophic changes. Inflammatory involvement has been demonstrated in past CRPS studies resulting in pain, swelling, and warmth. Currently, it is unknown whether spinal cord stimulation (SCS) has immunomodulatory properties. The aim of this study was to determine whether SCS has immunomodulatory properties in CRPS patients.
The primary outcome parameters are cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-15, IL-17, TNF-α, IFN-γ), chemokines (IP-10 and Eotaxin), and growth factors (VEGF, PDGFbb, and basic FGF) from interstitial fluid of artificial skin blisters before (T0-baseline without SCS) and after SCS therapy (T1-40 Hz standard frequency stimulation and T2-preferred frequency stimulation). Secondary outcome parameters were baseline demographics, CRPS signs, symptoms, and phenotype (inflammatory, vasomotor, dystonia, or neuropathic). Results were analyzed by means of a MANOVA repeated measures design.
After SCS, the expression of both pro- and anti-inflammatory cytokines decreased over time in both the CRPS affected extremity and the contralateral extremity. The levels of IP-10, Eotaxin, VEGF, and PDGFbb were also significantly reduced bilaterally. There were no significant changes in IL-6 and TNF-α before and after SCS. The sensory signs, symptoms, and phenotype improved after SCS.
SCS in CRPS patients attenuates T-cell activation, improves peripheral tissue oxygenation and decreases anti-angiogenetic activity which results in diminished endothelial dysfunction and improved bloodflow. The possible immunomodulatory effects of SCS opens new therapeutic possibilities in diseases with the involvement of the immune system and vasomotor disturbances, and requires further research on these mechanisms of action.
复杂性区域疼痛综合征（CRPS）的特征是持续疼痛与诱发事件不成比例、感觉异常、血管舒缩和出汗功能障碍以及运动和营养改变。过去关于CRPS的研究已证实存在炎症参与，导致疼痛、肿胀和发热。目前，尚不清楚脊髓刺激（SCS）是否具有免疫调节特性。本研究的目的是确定SCS在CRPS患者中是否具有免疫调节特性。
主要结局参数为细胞因子（白细胞介素-2、白细胞介素-4、白细胞介素-5、白细胞介素-6、白细胞介素-10、白细胞介素-12、白细胞介素-13、白细胞介素-15、白细胞介素-17、肿瘤坏死因子-α、干扰素-γ）、趋化因子（IP-10和嗜酸性粒细胞趋化因子）以及人工皮肤水疱组织间液中的生长因子（血管内皮生长因子、血小板衍生生长因子bb和碱性成纤维细胞生长因子），分别在SCS治疗前（T0-无SCS的基线）以及SCS治疗后（T1-40Hz标准频率刺激和T2-优选频率刺激）进行检测。次要结局参数为基线人口统计学数据、CRPS体征、症状和表型（炎症性、血管舒缩性、肌张力障碍性或神经性）。结果采用多变量方差分析重复测量设计进行分析。
SCS后，CRPS患侧肢体和对侧肢体中促炎和抗炎细胞因子的表达均随时间下降。双侧IP-10、嗜酸性粒细胞趋化因子、血管内皮生长因子和血小板衍生生长因子bb的水平也显著降低。SCS前后白细胞介素-6和肿瘤坏死因子-α无显著变化。SCS后感觉体征、症状和表型有所改善。
CRPS患者的SCS可减弱T细胞活化，改善外周组织氧合并降低抗血管生成活性，从而减少内皮功能障碍并改善血流。SCS可能的免疫调节作用为免疫系统和血管舒缩功能障碍相关疾病开辟了新的治疗可能性，需要对这些作用机制进行进一步研究。
