Pain and Rehabilitation Center, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
BMC Neurosci. 2021 Feb 1;22(1):6. doi: 10.1186/s12868-021-00608-5.
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.
神经病理性疼痛（NeuP）是一种感觉系统的复杂、衰弱性疾病，其中促炎和抗炎细胞因子及趋化因子的失调被认为起着关键作用。迄今为止，尚无普遍接受的 NeuP 诊断测试，且当前的治疗干预措施在疗效上存在不足。本研究旨在探究三种生物体液（唾液、血浆和脑脊液）在区分 NeuP 患者与健康对照者的中枢、全身和外周炎症特征方面的能力。
采用基于电化学发光检测法的多重免疫分析法，分析了 13 例周围性 NeuP 患者和 13 例健康对照者的唾液、血浆和脑脊液样本中的 71 种细胞因子、趋化因子和生长因子的浓度。NeuP 患者从鞘内注射 Ziconotide 的临床试验中招募（ClinicalTrials.gov 标识符 NCT01373983）。采用多元数据分析（主成分分析和正交偏最小二乘回归）来识别具有组间区分能力的蛋白和与疼痛强度相关的蛋白。具有投影变量重要性（VIP）值大于 1（与系数图中的 jack-knifed 置信区间不包括零相结合）的蛋白被认为具有统计学意义。
与健康对照组相比，我们发现 17 种细胞因子/趋化因子在 NeuP 患者中呈上调或下调。在这 17 种蛋白中，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，与疼痛强度相关性最强的重要蛋白存在于血浆中（VIP>1）。
对 NeuP 的炎症特征研究表明，用于组间区分的大多数显著蛋白存在于更微创的生物体液（唾液和血浆）中。在 NeuP 患者组中，还发现血浆中的蛋白与疼痛强度相关性最强。这些初步结果表明，在更易获取的唾液和血浆等生物体液中进行慢性周围性神经病理性疼痛的进一步生物标志物研究具有一定潜力，其中唾液中的 YKL-40 和 MIP-1α 可能是未来研究的重点，同时还应包括其他非神经病理性疼痛状态。
