Neuropathic pain (NeuP) is a complex, debilitating condition of the somatosensory system, where dysregulation between pro- and anti-inflammatory cytokines and chemokines are believed to play a pivotal role. As of date, there is no ubiquitously accepted diagnostic test for NeuP and current therapeutic interventions are lacking in efficacy. The aim of this study was to investigate the ability of three biofluids - saliva, plasma, and cerebrospinal fluid (CSF), to discriminate an inflammatory profile at a central, systemic, and peripheral level in NeuP patients compared to healthy controls. The concentrations of 71 cytokines, chemokines and growth factors in saliva, plasma, and CSF samples from 13 patients with peripheral NeuP and 13 healthy controls were analyzed using a multiplex-immunoassay based on an electrochemiluminescent detection method. The NeuP patients were recruited from a clinical trial of intrathecal bolus injection of ziconotide (ClinicalTrials.gov identifier NCT01373983). Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was used to identify proteins significant for group discrimination and protein correlation to pain intensity. Proteins with variable influence of projection (VIP) value higher than 1 (combined with the jack-knifed confidence intervals in the coefficients plot not including zero) were considered significant. We found 17 cytokines/chemokines that were significantly up- or down-regulated in NeuP patients compared to healthy controls. Of these 17 proteins, 8 were from saliva, 7 from plasma, and 2 from CSF samples. The correlation analysis showed that the most important proteins that correlated to pain intensity were found in plasma (VIP > 1). Investigation of the inflammatory profile of NeuP showed that most of the significant proteins for group separation were found in the less invasive biofluids of saliva and plasma. Within the NeuP patient group it was also seen that proteins in plasma had the highest correlation to pain intensity. These preliminary results indicate a potential for further biomarker research in the more easily accessible biofluids of saliva and plasma for chronic peripheral neuropathic pain where a combination of YKL-40 and MIP-1α in saliva might be of special interest for future studies that also include other non-neuropathic pain states.

中文翻译：

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严重神经性疼痛患者和健康对照者脑脊液、血浆和唾液的炎症特征——一项初步研究


神经性疼痛 (NeuP) 是一种复杂的、使体感系统衰弱的疾病，促炎性和抗炎性细胞因子以及趋化因子之间的失调被认为起着关键作用。迄今为止，还没有普遍接受的 NeuP 诊断测试，并且当前的治疗干预措施缺乏疗效。本研究的目的是调查三种生物流体——唾液、血浆和脑脊液（CSF）——与健康对照相比，区分 NeuP 患者中枢、全身和外周水平炎症特征的能力。使用基于电化学发光检测方法的多重免疫测定法分析了 13 名外周 NeuP 患者和 13 名健康对照者的唾液、血浆和脑脊液样本中 71 种细胞因子、趋化因子和生长因子的浓度。 NeuP 患者是从一项齐考诺肽鞘内推注临床试验中招募的（ClinicalTrials.gov 标识符 NCT01373983）。使用多变量数据分析（主成分分析和正交偏最小二乘回归）来识别对群体区分具有重要意义的蛋白质以及与疼痛强度相关的蛋白质。投影变量影响 (VIP) 值高于 1（与系数图中不包括零的折刀置信区间相结合）的蛋白质被认为是显着的。我们发现与健康对照相比，NeuP 患者中有 17 种细胞因子/趋化因子显着上调或下调。在这 17 种蛋白质中，8 种来自唾液，7 种来自血浆，2 种来自脑脊液样本。相关性分析表明，与疼痛强度相关的最重要的蛋白质存在于血浆中（VIP > 1）。 对 NeuP 炎症特征的研究表明，大多数用于群体分离的重要蛋白质都存在于侵入性较小的唾液和血浆生物液中。在 NeuP 患者组中，还发现血浆中的蛋白质与疼痛强度具有最高的相关性。这些初步结果表明，在更容易获得的唾液和血浆生物流体中治疗慢性周围神经性疼痛的生物标志物研究有潜力，其中唾液中 YKL-40 和 MIP-1α 的组合可能对未来的研究特别感兴趣，这些研究还包括其他研究非神经性疼痛状态。