Role of dopaminergic system in migraine

Abstract

IntroductionDespite recent advances, the pathogenesis of migraine is still unclear. The study of migraine pathophysiology includes the investigation of neurotransmitters and their potential role in the development of the attack. Scientific and clinical interest has focused on the role of 5-hydroxytryptamine (5-HT). However, the dopaminergic system also appears to play a major, still less recognized, role in migraine and dopamine (DA) can be considered the "second putative protagonist in headache" [1]. Several arguments suggest the involvement of DA in migraine pathophysiology [2,3].The dopaminergic system has a prominent role in motor and sensorial control, in modulating cognitive processes, and in the control of both prolactin and growth hormone secretion. Recently, a key role in the regulation of cerebral microcirculation has been demonstrated [4]. Based on their structure and pharmacological characteristics, five subtypes of DA receptors have been described: D1, D4 and D5 are Gs protein-coupled receptors, D2 is a Gi protein-coupled receptor, and the signal transducing system of D3 is not yet completely characterized.Evidence for hypersensitivity of the dopaminergic system in migraineThe theory that hypersensitivity of the DA system is involved in the pathogenesis of migraine has been supported by various authors on the basis of clinical, pharmacological and, recently, genetic evidence. Role of dopaminergic system in migraine Alessandra Cherchi Erminia Stochino Maria Paola Piccardi Maria Del ZompoAbstract The theory that hypersensitivity of dopamine (DA) system is involved in the pathogenesis of migraine has been supported by various authors on the basis of clinical, pharmacological and, recently, genetic evidence. Apomorphine, a selective and specific DA agonist, has a cerebral vasodilatatory effect and increases blood flow significantly in the middle cerebral artery in migraineurs. Processes from central DA neurons terminate in close contact with penetrating arterioles and cerebral capillaries in the cerebral cortex. This finding reaffirms the role of central neurogenic mechanisms in the regulation of the cerebral circulation and, we believe, further supports the major role of dopamine in the neurogenic mechanisms of migraine. Various studies have been carried out to verify the involvement of DA in migraine pathogenesis using molecular genetics as a tool. A positive association between the "dopaminergic" phenotype of migraine without aura and the D2 receptor gene has been found. To explain dopaminergic hypersensitivity in migraine without aura, we will study the genes encoding proteins involved in the signal transduction system.

Genetics of migraine and pharmacogenomics: some considerations

“…Several studies indicate that hypersensitivity of the dopaminergic system is implicated in the pathogenesis of migraine [ 50 ]. In fact, as reported above, an association between DRD2 gene and MA has been demonstrated [ 44 , 51 ].…”