Cytokines in Cerebrospinal Fluid and Chronic Pain in Humans: Past, Present, and Future.

IF 2.2 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Neuroimmunomodulation Pub Date : 2024-01-01 Epub Date: 2024-07-16 DOI:10.1159/000540324
Alexander H C Rosenström, Jan-Pieter Konsman, Eva Kosek
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Abstract

Background: That neuroimmune interaction occurs in chronic pain conditions has been established for over a century, since the discovery of neurogenic inflammation in the periphery. However, the central aspects of neuroimmune interactions have not been fully appreciated until the late 1900s, when a growing interest in how cytokines in the cerebrospinal fluid (CSF) might be relevant in chronic pain conditions emerged. Since then, the field has evolved, and nowadays neuroinflammation is considered to be involved in the pathophysiology of chronic pain. Whether or not pain conditions can be called "neuroinflammatory" is a matter of debate. This review summarizes the results from studies investigating cytokines in the CSF in various pain conditions, and critically discusses neuroimmune aspects of pain conditions using previously proposed hallmarks of neuroinflammation as a framework.

Summary: Fifty-two papers were summarized and their results evaluated according to (a) the level of the measured cytokines in patients compared to controls, and (b) the correlation between cytokine level and pain intensity. A subdivision based on pain type was also conducted for each of the 52 studies. A total of 49 proteins have been studied in at least 5 studies, 21 of which were upregulated in a majority of studies. IL-8 was specifically upregulated in a majority of studies of nociceptive pain conditions. Regarding correlation to pain intensity, there is a scarcity of data but 31 proteins were upregulated and correlated with pain in at least one study. Of these, 24 proteins were negatively correlated with pain, and 7 were positively correlated. None of the most studied cytokines, such as TNF, IL-1b, IL-6, IL-8, CCL2/MCP1, BDNF, or bNGF, were consistently correlated to pain.

Key messages: There is sufficient evidence to say that chronic pain conditions come with an upregulation of several cytokines. However, the majority of correlations to symptomatology seem to be negative, indicating that the cytokines might play a protective role that has not been broadly considered. Calling chronic pain conditions neuroinflammatory seems wrong; instead, a more suitable term for depicting the findings would, perhaps, be to talk about neuroimmune activation.

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脑脊液中的细胞因子与人类慢性疼痛--过去、现在和未来。
背景 自从发现外周神经源性炎症以来,神经免疫相互作用在慢性疼痛病症中的发生已经有一个多世纪的历史了。然而,直到 20 世纪末,人们才充分认识到神经免疫相互作用的核心方面,当时人们对脑脊液中的细胞因子如何与慢性疼痛病症相关的兴趣日益浓厚。此后,这一领域不断发展,如今神经炎症被认为与慢性疼痛的病理生理学有关。疼痛病症是否可以被称为 "神经炎症 "还存在争议。本综述总结了对各种疼痛情况下脑脊液中细胞因子的研究结果,并以之前提出的神经炎症特征为框架,批判性地讨论了疼痛情况的神经免疫方面。摘要 对 52 篇论文进行了总结,并根据 a) 与对照组相比,患者体内所测细胞因子的水平,以及 b) 细胞因子水平与疼痛强度之间的相关性,对论文结果进行了细分。此外,还根据疼痛类型对 52 项研究中的每一项进行了细分。至少有 5 项研究对 49 种蛋白质进行了研究,其中 21 种蛋白质在大多数研究中被上调。在大多数有关痛觉疼痛的研究中,IL8 都被特别上调。关于与疼痛强度的相关性,虽然数据很少,但至少有一项研究发现 31 种蛋白质上调并与疼痛相关。其中,24 种蛋白质与疼痛呈负相关,7 种呈正相关。研究最多的细胞因子(如 TNF、IL1b、IL6、IL8、CCL2/MCP1、BDNF 或 bNGF)均与疼痛无关。关键信息 有足够的证据表明,慢性疼痛会导致多种细胞因子上调。然而,大多数细胞因子与症状的相关性似乎是负相关的,这表明细胞因子可能起到保护作用,而这一点尚未得到广泛考虑。将慢性疼痛称为神经炎症似乎是错误的;相反,描述研究结果的更合适的术语或许是神经免疫激活。
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来源期刊
Neuroimmunomodulation
Neuroimmunomodulation 医学-免疫学
CiteScore
3.60
自引率
4.20%
发文量
35
审稿时长
>12 weeks
期刊介绍: The rapidly expanding area of research known as neuroimmunomodulation explores the way in which the nervous system interacts with the immune system via neural, hormonal, and paracrine actions. Encompassing both basic and clinical research, ''Neuroimmunomodulation'' reports on all aspects of these interactions. Basic investigations consider all neural and humoral networks from molecular genetics through cell regulation to integrative systems of the body. The journal also aims to clarify the basic mechanisms involved in the pathogenesis of the CNS pathology in AIDS patients and in various neurodegenerative diseases. Although primarily devoted to research articles, timely reviews are published on a regular basis.
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