Abstract
BackgroundMedication overuse headache (MOH) is a common and debilitating disorder characterized by generation, perpetuation, and persistence of intense chronic migraine, caused by overuse of analgesics, triptans, or other acute headache compounds. It has been suggested that MOH could share some pathogenetic mechanisms with other kinds of drug addiction. In this regard, histone deacetylases 3 (HDAC3) seems to have a role in the memory processes involved in extinction of drug-seeking behavior in animal models. HDAC3 is inhibited by sodium valproate, a drug with proven efficacy in MOH. Recent evidence suggests an involvement of genetic factors in predisposition to medication overuse.ResultsIn this association study, we sequenced all exons, intron/exon junctions, and 3′-5′UTR regions of HDAC3 in 23 MOH patients to investigate its role in medication overuse. Associations between genotypes with continuous and dichotomous clinical characteristics were tested by multivariate analysis and Fisher’s exact test, respectively.Sequencing of HDAC3 revealed six single-nucleotide polymorphisms. The G allele of rs2530223 was significantly associated with the number of acute medications/month used and with the number of days/month in which medications were used (p = 0.006 and p = 0.007, respectively), but neither with headache frequency or intensity. None of the single-nucleotide polymorphisms (SNPs) was associated with clinical characteristics or response to sodium valproate.ConclusionsHDAC3 could be implicated in excessive medication consumption in MOH patients. Our preliminary findings provide support for the need of further investigation on larger independent samples to confirm and extend the role of HDAC3 in medication overuse headache.
Highlights
Medication overuse headache (MOH) is a common and debilitating disorder characterized by generation, perpetuation, and persistence of intense chronic migraine, caused by overuse of analgesics, triptans, or other acute headache compounds
Sequencing of the histone deacetylases 3 (HDAC3) gene revealed five intronic single-nucleotide polymorphisms (SNP) and the synonym variant located in exon 3, rs2530223 (Fig. 1)
All SNPs were already present in public databases (UCSC Genome Bioinformatics; NCBI), and no new variants were identified in our patients
Summary
Medication overuse headache (MOH) is a common and debilitating disorder characterized by generation, perpetuation, and persistence of intense chronic migraine, caused by overuse of analgesics, triptans, or other acute headache compounds. It has been suggested that MOH could share some pathogenetic mechanisms with other kinds of drug addiction. In this regard, histone deacetylases 3 (HDAC3) seems to have a role in the memory processes involved in extinction of drug-seeking behavior in animal models. A neuroimaging study with 18F-fluorodeoxyglucose positron-emission tomography in MOH patients showed that a number of dysmetabolic brain areas involved in pain-processing recovered after withdrawal of medication, while long-lasting dysfunction was observed in orbitofrontal cortex [10], an area suggested to be involved in drug dependence and addiction [11]. On the basis of this evidence, it has been speculated that MOH shares some pathogenetic mechanisms with other kinds of drug addiction [13, 14]
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