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Chronic headache is a topical problem of neurology, psychiatry and general practice. The medication-overuse headache (MOH) is one of the leading pathologies in the structure of chronic headache. However, early diagnosis of the MOH is challenging. We analyzed potential proteomic biomarkers of serum and urine in patients with MOH., Methods: We searched PubMed, Springer, Scopus, Web of Science, ClinicalKey, and Google Scholar databases for English publications over the past 10 years using keywords and their combinations., Results: We found and analyzed seven studies that met the search criteria for the purpose of the review, including 24 serum proteomic biomarkers and 25 urine proteomic biomarkers of MOH. Moreover, the candidate genes and locus of the studied serum (vitamin D-binding protein, lipocalin-type prostaglandin D2 synthase, apolipoprotein E, etc.) and urine proteomic biomarkers (uromodulin, alpha-1-microglobulin, zinc-alpha-2-glycoprotein, etc.) of MOH are presented in this review., Conclusions: The serum and urine proteomic biomarkers of MOH can potentially help with the identification of patients with MOH development. Due to the relevance of the problem, the authors believe that further investigation of the MOH proteomic biomarkers in different ethnic and racial groups of patients with primary headache is necessary. In addition, it is important to investigate whether medications of different drug classes influence the levels of serum and urine proteomic biomarkers.

Migraine (M) and arterial hypertension (AH) are very common diseases. Today, there are a number of studies confirming and explaining their comorbidity. We searched PubMed, Springer, Scopus, Web of Science, Clinicalkeys, and Google Scholar databases for full-text English publications over the past 15 years using keywords and their combinations. The present review provides a synthesis of information about single nucleotide variants (SNVs) of NOS1 , NOS2 , and NOS3 genes involved in the development of M and essential AH. The results of studies we have discussed in this review are contradictory, which might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical environments. Despite a high prevalence of the M and AH phenotype, its genetic markers have not yet been sufficiently studied. Specifically, there are separate molecular genetic studies aimed to identify SNVs of NOS1 , NOS2 , and NOS3 genes responsible for the development of M and those responsible for the development of AH. However, these SNVs have not been studied in patients with the phenotype of M and AH. In this review, we identify the SNVs that would be the most interesting to study in this aspect. Understanding the role of environmental factors and genetic predictors will contribute to a better diagnostics and exploration of new approaches to pathogenetic and disease-modifying treatment of the M and AH phenotype.

Patients with tension-type headache (TTH) have an increased risk of developing arterial hypertension (AH), while hypertensive subjects do seem to have an increased risk of TTH. We searched for full-text English publications in databases using keywords and combined word searches over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we summed up the single nucleotide variants (SNVs) of Nitric Oxide Synthases ( NOSs ) genes involved in the development of essential AH and TTH. The results of studies we discussed in this review are contradictory. This might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors remains understudied. This makes the issue interesting for researchers, as understanding these mechanisms can contribute to a search for new approaches to pathogenetic and disease-modifying treatment of the AH and TTH phenotype. New drugs against AH and TTH can be based on inhibition of nitric oxide (NO) production, blockade of steps in the NO-cGMP pathway, or NO scavenging. Indeed, selective neuronal NOS (n-NOS) and inducible NOS (i-NOS) inhibitors are already in early clinical development.

Melatonin is the most well-known regulator of the circadian rhythms of all living organisms and the main substrate synthesized at night. There are 4 stages in the synthesis of melatonin. This review focuses on the 2nd, 3rd, and 4th stages. The review is aimed at analyzing publications on molecular genetic association studies on the role of single nucleotide polymorphisms (SNPs) of the DDC ( AADC ), AANAT and ASMT genes encoding melatonin synthesis enzymes in the pathogenesis of socially significant neuropsychiatric disorders in humans. The authors analyzed the available full-text articles from several databases, as well as materials from electronic resources. Search depth was 15 years. The analysis of these studies over the past decade show the association of some SNPs of the studied genes with the risk of neuropsychiatric disorders such as delayed sleep phase disorder, attention deficit hyperactivity disorder, autism spectrum disorder, migraine, Parkinson's disease, depression, anxiety, bipolar-affective disorder, schizophrenia.

Arterial hypertension (AH) and exertional headache (EHA) are comorbidities. The article presents a nonsystematic review focused on studying the AH+EHA phenotype. The authors addressed the history of studying the phenotype, several theories about its pathophysiological causes (psychosomatic, neuroanatomical, and baroreflector). The protective "hypertension-associated hypoalgesia" phenotype, a mechanism of its change in AH chronization, and difficulties of differential diagnosis are described. The AH+EHA phenotype requires further study since its incidence is quite high. This will allow developing an individualized approach in prevention and treatment of EHA attacks, decreasing the risk of life-threatening cardiovascular complications, and avoiding iatrogenic complications in patients with AH. The main way to prevent the development of AH+EHA phenotype is patient's compliance, which can be provided by using combination hypotensive drugs to reduce the number of pills and dosing. It is important to take into account possible adverse reactions of the nervous system (medication-overuse headache or EHA aggravation). Considering these conditions, the drug Triplixam can be used for prevention of complications in the AH+EHA phenotype. Triplixam is a fixed triple combination of amlodipine/indapamide/perindopril, and its individual components have low and medium risk for development of headache.

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