OC-02 | Role of specific microRNAs in cluster headache: association with disease phenotype and neuropeptide levels

A. Solfrizzi,^1,2 F. Cammarota,^1,2 R. De Icco,^1,2 F. Bighiani,^1,2 M. Corrado,² G. Vaghi,^1,2 A. Antoniazzi,^1,2 V. Grillo,^1,2 M. Giraudo,^1,2 B. Agostini,^1,2 R. Greco,² C. Demartini,^1,2 M. Francavilla,^1,2 S. Franchini,^1,2 M. Allena,² G. Sances,² C. Tassorelli¹ | ¹Department of Brain and Behavioral Sciences, University of Pavia; ²Headache Science and Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy

Background: Increasing evidence is supporting the role of epigenetic mechanisms in primary headaches. MicroRNAs (miRNAs) may be involved in pain generation and evolution in chronic migraine, while their involvement in cluster headache (CH) is still far from clear. The primary aim of this study was to assess the expression of miRNAs in episodic CH, evaluated during the active (AeCH) and remission (ReCH) phase, in chronic CH (cCH), and in healthy controls (HCs).

Methods: We assessed gene expression of miR-382-5p, miR-34a-5p, and miR-155 in blood mononuclear cells (PBMCs) isolated from peripheral blood sampling after night fasting. miRNAs expression was defined as Relative Quantification (RQ) to U6 housekeeping gene. AeCH and cCH patients were evaluated outside of the acute cluster headache attack.

Results: The study population included 36 AeCH patients (mean age: 47.30 ± 11.14 years, 29 males), 26 ReCH patients (mean age 46.92 ± 11.77 years, 21 males), 17 cCH patients (mean age: 52.06 ± 14.5 years, 14 males) e 27 HCs (mean age: 44.55 ± 15.07 years, 15 males). Gene expression of the three analyzed miRNA was higher in CH participants when compared to HCs (miR-382-5p, CH: 1.28 ± 0.58 RQ vs. HC: 0.33 ± 0.14 RQ; miR-155, CH: 1.40 ± 0.51 RQ vs. HC: 0.45 ± 0.09; miR-34-a, CH: 1.38 ± 0.57 RQ vs. HC: 0.51 ± 0.20 RQ, p<0.05 for all comparisons). At post-hoc analyses, miR-382-5p and miR-155 gene expression was higher in AeCH when compared to ReCH (miR-382-5p, AeCH: 1.68 ± 0.85 RQ vs. ReCH: 1.20 ± 0.27 RQ, p=0.005; miR-155, AeCH: 1.69 ± 0.48 RQ vs. ReCH: 1.31 ± 0.35 RQ, p=0.015). No differences between the active and remission phases were observed for miR-34a expression. No differences among cCH, AeCH and ReCH were found for all the tested miRNAs (in cCH: miR-382-5p: 1.202 ± 0.269, miR-34a-5p: 1.213 ± 0.322; miR-155: 1.332 ± 0.534).

Conclusion: Our data supports an involvement of specific miRNAs in the pathophysiology of cluster headache. Considering their well-known involvement in other primary headaches, it is conceivable that these miRNAs do not represent a CH biomarker.