Exploratory study for identifying systemic biomarkers that correlate with pain response in patients with intervertebral disc disorders.
Exploratory study for identifying systemic biomarkers that correlate with pain response in patients with intervertebral disc disorders.
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DOI：
10.1007/s12026-015-8709-2
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发表时间：
2015-12
影响因子：
4.4
通讯作者：
Chahine NO
中科院分区：
文献类型：
--
作者：
Weber KT;Satoh S;Alipui DO;Virojanapa J;Levine M;Sison C;Quraishi S;Bloom O;Chahine NO
驱动椎间盘损伤和腰痛（LBP）的分子事件可能先于疾病发作的临床表现，并可能导致有害的长期影响，如残疾。生物标志物作为病理过程的客观分子指标。本研究的目的是确定全身生化因素作为预测硬膜外类固醇注射（ESI）治疗LBP的反应。由于炎症在LBP中起着关键作用，因此本初步研究调查了ESI对48种炎症生化因子的全身水平的影响（细胞因子，趋化因子和生长因子），并检查生化因子水平与椎间盘突出症（DH）患者疼痛或残疾或其他诊断之间的关系（其他Dx）导致腰痛，包括椎管狭窄（SS）和退行性椎间盘疾病（DDD）。研究参与者（n = 16）从背痛管理实践中招募。在治疗前和治疗后7 - 10天收集疼痛数字评分（NRS）、奥斯韦斯特里残疾指数（ODI）和血液样本。使用商业多重测定法测定血液样品的炎症介质。比较治疗前后的介体水平，以研究临床和生化结果之间的潜在相关性。我们的研究结果表明，一个单一的ESI显着降低全身水平的SCGF-β和IL-2。所有受试者的疼痛改善均与趋化因子（MCP-1、TNF）、造血祖细胞因子（SCGF-β）以及参与血管生成/纤维化（HGF）、伤害感受（SCF、IFN-α2）和炎症（IL-6、IL-10、IL-18、TRAIL）的因子的变化相关。生化介质的水平根据腰痛的诊断而变化，疼痛反应和全身介质从治疗前到治疗后的变化取决于诊断队列。在DH队列中，IL-17和VEGF水平在治疗后显著降低。在其他Dx队列中，治疗后IL-2 R α、IL-3和SCGF-β水平显著降低。为了确定介质变化是否与疼痛有关，进行疼痛评分变化与介质水平变化之间的相关性。患有DH的受试者表现出涉及造血因子（SCGF-β、GM-CSF）的特征，而患有其他Dx的受试者表现出涉及趋化因子（MCP-1、VEGF）和血管生成因子（HGF、VEGF）的生物标志物特征。我们的研究结果提供的证据表明，LBP患者的全身生化因素因诊断而异，对治疗的疼痛反应与每个诊断组中独特的生化反应相关。未来有必要进行更大受试者队列的基于假设的研究，以证实这项初步探索性研究的结果。
Molecular events that drive disc damage and low back pain (LBP) may precede clinical manifestation of disease onset and can cause detrimental long-term effects such as disability. Biomarkers serve as objective molecular indicators of pathological processes. The goal of this study is to identify systemic biochemical factors as predictors of response to treatment of LBP with epidural steroid injection (ESI). Since inflammation plays a pivotal role in LBP, this pilot study investigates the effect of ESI on systemic levels of 48 inflammatory biochemical factors (cytokines, chemokines, and growth factors) and examines the relationship between biochemical factor levels and pain or disability in patients with disc herniation (DH), or other diagnoses (Other Dx) leading to low back pain, which included spinal stenosis (SS) and degenerative disc disease (DDD). Study participants (n = 16) were recruited from a back pain management practice. Pain numerical rating score (NRS), Oswestry Disability Index (ODI), and blood samples were collected pre- and at 7 to 10 days post-treatment. Blood samples were assayed for inflammatory mediators using commercial multiplex assays. Mediator levels were compared pre- and post-treatment to investigate the potential correlations between clinical and biochemical outcomes. Our results indicate that a single ESI significantly decreased systemic levels of SCGF-β and IL-2. Improvement in pain in all subjects was correlated with changes in chemokines (MCP-1, MIG), hematopoietic progenitor factors (SCGF-β), and factors that participate in angiogenesis/fibrosis (HGF), nociception (SCF, IFN-α2), and inflammation (IL-6, IL-10, IL-18, TRAIL). Levels of biochemical mediators varied based on diagnosis of LBP, and changes in pain responses and systemic mediators from pre- to post-treatment were dependent on the diagnosis cohort. In the DH cohort, levels of IL-17 and VEGF significantly decreased post-treatment. In the Other Dx cohort, levels of IL-2Rα, IL-3, and SCGF-β significantly decreased post-treatment. In order to determine whether mediator changes were related to pain, correlations between change in pain scores and change in mediator levels were performed. Subjects with DH demonstrated a profile signature that implicated hematopoiesis factors (SCGF-β, GM-CSF) in pain response, while subjects with Other Dx demonstrated a biomarker profile that implicated chemokines (MCP-1, MIG) and angiogenic factors (HGF, VEGF) in pain response. Our findings provide evidence that systemic biochemical factors in patients with LBP vary by diagnosis, and pain response to treatment is associated with a unique profile of biochemical responses in each diagnosis group. Future hypothesis-based studies with larger subject cohorts are warranted to confirm the findings of this pilot exploratory study.