Background: Emerging evidence highlights the role of microRNAs (miRNAs) in epigenetic mechanisms related to migraine pain. The expression of miR-382-5p and miR-34a is higher in serum and peripheral blood mononuclear cells of people with migraine, but limited data is available regarding their possible alteration in other cell subtypes. Several lines of evidence support a monocyte dysfunction in migraine pathophysiology. To gain deeper insights into cell-specific miRNAs expression in migraine individuals with different disease severity, this study aims to determine the expression levels of miR-34a and miR-382-5p in monocytes. Methods: This cross-sectional, controlled study included 47 participants with episodic migraine (EM, 72.3% females, 41.4 ± 10.7 years), 32 with chronic migraine with medication overuse (CM-MO, 81.3% females, 46.1 ± 10.9 years) and 30 healthy controls (HCs, 66.7% females, 42.9 ± 14.8 years). We assessed interictal monocyte-specific miR-382-5p and miR-34a expression by qRT-PCR, normalizing the expression with U6 RNA (relative quantification - RQ). Results: miR-382-5p monocytic expression was higher in EM (4.21 ± 1.41 RQ) and CM-MO (6.80 ± 4.37 RQ) when compared to HCs (2.02 ± 0.64 RQ) (p = 0.005 for all comparisons). miR-34a monocytic expression was higher in EM (4.50 ± 1.62 RQ) and CM-MO (6.47 ± 1.87 RQ) when compared to HCs (1.94 ± 0.81 RQ, p = 0.005 for all comparisons). Expression of miR-382-5p and miR-34a were higher in CM-MO when compared to EM (p = 0.005 for both comparisons). After adjusting for age, sex, ongoing preventive medications, presence of anxiety or depressive symptoms, and smoking habit, a logistic regression model confirmed the differences in the monocytic expression of miR-34a and miR-382-5p between EM and CM-MO participants. Conclusions: Our findings underscore the relevance of miR-34a and miR-382-5p in migraine pathophysiology, as evidenced by their altered expression in monocytes from migraine participants compared to HCs. These miRNAs were also associated with disease severity, being higher in CM-MO when compared to EM individuals. Trial Registration: The study protocol was registered at ClinicalTrials.gov (NCT05891808).
miR-382-5p and miR-34a in migraine: Expression in monocytes and a post-hoc exploratory comparison with expression in peripheral blood mononuclear cells
Bighiani, Federico;Demartini, Chiara;Francavilla, Miriam;Facchetti, Sara;Vaghi, Gloria;Martinelli, Daniele;Corrado, Michele;Ghiotto, Natascia;Bottiroli, Sara;Cammarota, Francescantonio;Antoniazzi, Alessandro;Grillo, Valentina;Tassorelli, Cristina;De Icco, Roberto
2025-01-01
Abstract
Background: Emerging evidence highlights the role of microRNAs (miRNAs) in epigenetic mechanisms related to migraine pain. The expression of miR-382-5p and miR-34a is higher in serum and peripheral blood mononuclear cells of people with migraine, but limited data is available regarding their possible alteration in other cell subtypes. Several lines of evidence support a monocyte dysfunction in migraine pathophysiology. To gain deeper insights into cell-specific miRNAs expression in migraine individuals with different disease severity, this study aims to determine the expression levels of miR-34a and miR-382-5p in monocytes. Methods: This cross-sectional, controlled study included 47 participants with episodic migraine (EM, 72.3% females, 41.4 ± 10.7 years), 32 with chronic migraine with medication overuse (CM-MO, 81.3% females, 46.1 ± 10.9 years) and 30 healthy controls (HCs, 66.7% females, 42.9 ± 14.8 years). We assessed interictal monocyte-specific miR-382-5p and miR-34a expression by qRT-PCR, normalizing the expression with U6 RNA (relative quantification - RQ). Results: miR-382-5p monocytic expression was higher in EM (4.21 ± 1.41 RQ) and CM-MO (6.80 ± 4.37 RQ) when compared to HCs (2.02 ± 0.64 RQ) (p = 0.005 for all comparisons). miR-34a monocytic expression was higher in EM (4.50 ± 1.62 RQ) and CM-MO (6.47 ± 1.87 RQ) when compared to HCs (1.94 ± 0.81 RQ, p = 0.005 for all comparisons). Expression of miR-382-5p and miR-34a were higher in CM-MO when compared to EM (p = 0.005 for both comparisons). After adjusting for age, sex, ongoing preventive medications, presence of anxiety or depressive symptoms, and smoking habit, a logistic regression model confirmed the differences in the monocytic expression of miR-34a and miR-382-5p between EM and CM-MO participants. Conclusions: Our findings underscore the relevance of miR-34a and miR-382-5p in migraine pathophysiology, as evidenced by their altered expression in monocytes from migraine participants compared to HCs. These miRNAs were also associated with disease severity, being higher in CM-MO when compared to EM individuals. Trial Registration: The study protocol was registered at ClinicalTrials.gov (NCT05891808).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
