Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Kiel Campus, Kiel, Germany.
Department of Neurology, University Hospital Schleswig-Holstein, Kiel Campus, Kiel, Germany.
Pain. 2021 Sep 1;162(9):2366-2375. doi: 10.1097/j.pain.0000000000002274.
During the past few years, the research of chronic neuropathic pain has focused on neuroinflammation within the central nervous system and its impact on pain chronicity. As part of the ERA-Net NEURON consortium, we aimed to identify immune cell patterns in the cerebrospinal fluid (CSF) of patients with herpes zoster neuralgia and patients with polyneuropathy (PNP), which may contribute to pain chronicity in these neuropathic pain conditions. Cerebrospinal fluid of 41 patients (10 herpes zoster and 31 PNP) was analyzed by flow cytometry identifying lymphocyte subsets: CD4+ (T-helper cells), CD8+ (cytotoxic T cells), CD19+ (B cells), and CD56+ (natural killer [NK]) cells. At baseline and at follow-up, the somatosensory phenotype was assessed with quantitative sensory testing. In addition, the patients answered epidemiological questionnaires and the PainDETECT questionnaire. Immune cell profiles and somatosensory profiles, as well as painDETECT questionnaire scores, were analyzed and correlated to determine specific immune cell patterns, which contribute to chronic pain. We found a negative correlation (P = 0.004, r = -0.596) between the frequency of NK cells and mechanical pain sensitivity (MPS), one of the most relevant quantitative sensory testing markers for central sensitization; a high frequency of NK cells correlated with low MPS. The analysis of the individual follow-up showed a worsening of the pain condition if NK-cell frequency was low. Low NK-cell frequency is associated with signs of central sensitization (MPS), whereas high NK-cell frequency might prevent central sensitization. Therefore, NK cells seem to play a protective role within the neuroinflammatory cascade and may be used as a marker for pain chronicity.
在过去的几年中，慢性神经性疼痛的研究集中在中枢神经系统的神经炎症及其对疼痛持续性的影响。作为 ERA-Net NEURON 联盟的一部分，我们旨在确定带状疱疹神经痛患者和多发性神经病（PNP）患者脑脊液（CSF）中的免疫细胞模式，这些模式可能导致这些神经性疼痛疾病的疼痛持续性。通过流式细胞术分析了 41 名患者（10 名带状疱疹和 31 名 PNP）的脑脊液，以鉴定淋巴细胞亚群：CD4+（辅助性 T 细胞）、CD8+（细胞毒性 T 细胞）、CD19+（B 细胞）和 CD56+（自然杀伤[NK]）细胞。在基线和随访时，使用定量感觉测试评估躯体感觉表型。此外，患者回答了流行病学问卷和 PainDETECT 问卷。分析和相关免疫细胞图谱和躯体感觉图谱以及 PainDETECT 问卷评分，以确定特定的免疫细胞模式，这些模式有助于慢性疼痛。我们发现 NK 细胞的频率与机械痛觉敏感性（MPS）呈负相关（P = 0.004，r = -0.596），MPS 是用于中枢敏感化的最相关定量感觉测试标志物之一；NK 细胞的高频率与低 MPS 相关。对个体随访的分析表明，如果 NK 细胞频率较低，则疼痛状况会恶化。低 NK 细胞频率与中枢敏感化（MPS）的迹象相关，而高 NK 细胞频率可能防止中枢敏感化。因此，NK 细胞似乎在神经炎症级联反应中发挥保护作用，并可用作疼痛持续性的标志物。
