Experimental and Clinical Investigation of Cytokines in Migraine: A Narrative Review

Int J Mol Sci. 2023 May 6;24(9):8343. doi: 10.3390/ijms24098343.


The role of neuroinflammation in the pathophysiology of migraines is increasingly being recognized, and cytokines, which are important endogenous substances involved in immune and inflammatory responses, have also received attention. This review examines the current literature on neuroinflammation in the pathogenesis of migraine. Elevated TNF-α, IL-1β, and IL-6 levels have been identified in non-invasive mouse models with cortical spreading depolarization (CSD). Various mouse models to induce migraine attack-like symptoms also demonstrated elevated inflammatory cytokines and findings suggesting differences between episodic and chronic migraines and between males and females. While studies on human blood during migraine attacks have reported no change in TNF-α levels and often inconsistent results for IL-1β and IL-6 levels, serial analysis of cytokines in jugular venous blood during migraine attacks revealed consistently increased IL-1β, IL-6, and TNF-α. In a study on the interictal period, researchers reported higher levels of TNF-α and IL-6 compared to controls and no change regarding IL-1β levels. Saliva-based tests suggest that IL-1β might be useful in discriminating against migraine. Patients with migraine may benefit from a cytokine perspective on the pathogenesis of migraine, as there have been several encouraging reports suggesting new therapeutic avenues.

Keywords: IL-1β; TNF-α; cortical spreading depolarization; cytokines; migraine; mouse models; neuroinflammation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokines*
  • Female
  • Humans
  • Interleukin-6
  • Male
  • Mice
  • Migraine Disorders* / etiology
  • Neuroinflammatory Diseases
  • Tumor Necrosis Factor-alpha


  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-6

Grants and funding

This research received no external funding.