Hsa-miR-34a-5p and hsa-miR-375 as Biomarkers for Monitoring the Effects of Drug Treatment for Migraine Pain in Children and Adolescents: A Pilot Study.

Luca Gallelli,Maria Cristina Caroleo,Antonio Verano,Vincenzo Guidetti,Luca Sammartino,Angelo Montana,Fancesco Peltrone,Serena Siviglia,Stefania Zampogna,Giovambattista De Sarro,Erika Cione,Giulio Di Mizio,Domenico Chirchiglia

doi:10.3390/jcm8070928

Abstract

MicroRNAs (miRs) have emerged as biomarkers of migraine disease in both adults and children. In this study we evaluated the expression of hsa-miR-34a-5p and hsa-miR-375 in serum and saliva of young subjects (age 11 ± 3.467 years) with migraine without aura (MWA), while some underwent pharmacological treatment, and healthy young subjects were used as controls. miRs were determined using the qRT-PCR method, and gene targets of hsa-miR-34a-5p and hsa-miR-375 linked to pain-migraine were found by in silico analysis. qRT-PCR revealed comparable levels of hsa-miRs in both blood and saliva. Higher expression of hsa-miR-34a-5p and hsa-miR-375 was detected in saliva of untreated MWAs compared to healthy subjects (hsa-miR-34a-5p: p < 0.05; hsa-miR-375 p < 0.01). Furthermore, in MWA treated subjects, a significant decrease of hsa-miR-34a-5p and of hsa-miR-375 was documented in saliva and blood compared to MWA untreated ones. Altogether, these findings suggested thathsa-miR-34a-5p and hsa-miR-375 are expressed equally in blood and saliva and that they could be a useful biomarker of disease and of drug efficacy in patients with MWA.

Highlights

Migraine is a common disabling primary headache disorder in both adult and children [1]
In this study we evaluated the expression of hsa-miR-34a-5p and hsa-miR-375 in serum and saliva of treated and untreated children with migraine without aura
History showed that 13 of 24 subjects (54.2%) had a positive familiality with headache and this was more common in females (83.3%); patients enrolled in the treated-group had mild-moderate pain visual analogue scale (VAS < 5) while subjects in untreated-group had severe pain (VAS > 8) (Table 1)

Summary

Introduction

Migraine is a common disabling primary headache disorder in both adult and children [1]. NSAIDs represent the first line treatment for acute migraine attack [2,3,4], but their use can induce chronic migraines and adverse drug reactions (ADRs), in children or adolescents [5,6]. Identification of specific biomarkers of disease and of drug efficacy in children and adolescents with migraines have clinical, forensic and ethical issues. In spite of this concern, some authors have proposed the use of biomarkers to guide the choice of treatment, to monitor the improvement or worsening of migraine symptoms during the treatment and to determine the appropriate therapeutic regimen in order to avoid drug/dietary supplements ADRs or inefficacy [7,8,9]. CGRP has a short half-life (about 7 min) [16,17] and could be liable for false negative results

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Results

Conclusion