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

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.
In this review, we have summarized the current evidence on signs of dysregulated cytokines, a family of proteins important for the function of both immune cells and nerve cells, in spinal fluid of chronic pain populations. Chronic pain is a complex entity, and alterations in cytokine activity has been proposed as a potential way in which some disease mechanisms might be mediated or maintained. In this review, we found 21 cytokines to be upregulated in chronic pain populations compared to controls. However, their association with pain intensity remains unclear. The few studies that have assessed cytokine levels in relation to pain intensity have found that a majority of cytokines that show some form of association to pain are negatively correlated to pain intensity, indicating possible pain-relieving roles of cytokine activity in the CSF.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Cytokines in Cerebrospinal Fluid and Chronic Pain in Humans: Past, Present, and Future ; volume:31 ; number:1 ; year:2024 ; pages:157-172 ; extent:16 ; Neuroimmunomodulation ; 31, Heft 1 (2024), 157-172 (gesamt 16)

Beteiligte, Orts- und Zeitangaben

• Urheber: Rosenström, Alexander H.C. ; Konsman, Jan-Pieter ; Kosek, Eva

Weitere Informationen

• DOI: 10.1159/000540324
• URN: urn:nbn:de:101:1-2412260218455.951386725412
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:36 MESZ