Expression of miR-155 in monocytes of people with migraine: association with phenotype, disease severity and inflammatory profile
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Updated: Jun 30, 2026
Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro
Published on: June 13, 2011
Rosaria Greco1, Federico Bighiani2,1, Chiara Demartini1
1Headache Science & Neurorehabilitation Unit, IRCCS Mondino Foundation, Via Mondino 2, Pavia, 27100, Italy.
Background:
miR-155 is involved in the generation and maintenance of inflammation and pain, endothelial function and immune system homeostasis, all functions that are relevant for migraine. The present study aims to assess the levels of miR-155 in migraine subtypes (episodic and chronic) in comparison to age- and sex-matched healthy controls.
Methods:
This is a cross-sectional, controlled, study involving three study groups: I) episodic migraine (n = 52, EM), II) chronic migraine with medication overuse (n = 44, CM-MO), and III) healthy controls (n = 32, HCs). We assessed the interictal gene expression levels of miR-155, IL-1β, TNF-α, and IL-10 in peripheral blood monocytes using rtPCR. The monocytic differentiation toward the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes was assessed in circulating monocytes with flow cytometry analysis and cell sorting.
Results:
miR-155 gene expression was higher in CM-MO group (2.68 ± 2.47 Relative Quantification - RQ) when compared to EM group (1.46 ± 0.85 RQ, p = 0.006) and HCs (0.44 ± 0.18 RQ, p = 0.001). In addition, miR-155 gene expression was higher in EM group when compared to HCs (p = 0.001). A multivariate analysis confirmed the difference between EM and CM-MO groups after correction for age, sex, smoking habit, preventive treatment, aura, presence of psychiatric or other pain conditions. We found higher gene expression of IL-1β, TNF-α, and lower gene expression of IL-10 in migraine participants when compared to HCs (p = 0.001 for all comparisons). TNF-α and IL-10 genes alterations were more prominent in CM-MO when compared to EM participants (p = 0.001). miR-155 positively correlated with IL-1β (p = 0.001) and TNF-α (p = 0.001) expression levels. Finally, in people with CM-MO, we described an up-regulated percentage of events in both M1 and M2 monocytic profiles.
Conclusions:
Our study shows for the first time a specific profile of activation of miR-155 gene expression levels in monocytes of selected migraine subpopulations, more pronounced in subjects with CM-MO. Interestingly, mir-155 expression correlated with markers of activation of the inflammatory and immune systems. The CM-MO subpopulation showed a peculiar increase of both pro-inflammatory and anti-inflammatory monocytes which worths further investigation.
Trial Registration:
www.
Clinicaltrials:
gov . (NCT05891808).
Insights
MicroRNA-155 (miR-155) gene expression is elevated in chronic migraine with medication overuse (CM-MO) and episodic migraine (EM) patients compared to controls. This suggests miR-155 plays a role in migraine pathogenesis, particularly in CM-MO.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- MicroRNA-155 (miR-155) is implicated in inflammation, immune homeostasis, and endothelial function, processes relevant to migraine.
- Assessing miR-155 levels in different migraine subtypes can elucidate its role in the condition.
Purpose of the Study:
- To evaluate miR-155 gene expression levels in patients with episodic migraine (EM) and chronic migraine with medication overuse (CM-MO).
- To compare these levels against age- and sex-matched healthy controls (HCs).
- To investigate the correlation between miR-155 and inflammatory markers (IL-1β, TNF-α, IL-10) and monocytic phenotypes (M1/M2).
Main Methods:
- Cross-sectional study with three groups: EM (n=52), CM-MO (n=44), and HCs (n=32).
- Quantitative real-time PCR (rtPCR) was used to measure interictal gene expression of miR-155, IL-1β, TNF-α, and IL-10 in peripheral blood monocytes.
- Flow cytometry and cell sorting assessed monocytic differentiation into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes.
Main Results:
- miR-155 gene expression was significantly higher in CM-MO and EM groups compared to HCs.
- miR-155 expression was most pronounced in the CM-MO group.
- Elevated IL-1β and TNF-α, and reduced IL-10 expression were observed in migraineurs versus HCs, with more prominent alterations in CM-MO.
- miR-155 positively correlated with IL-1β and TNF-α.
- CM-MO patients exhibited an increased percentage of both M1 and M2 monocytes.
Conclusions:
- This study reveals a distinct miR-155 gene expression profile in monocytes of migraine subpopulations, particularly elevated in CM-MO.
- miR-155 expression correlates with inflammatory and immune system activation markers.
- The increased presence of both pro- and anti-inflammatory monocytes in CM-MO warrants further investigation.
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