Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied by gastrointestinal and visual disorders. Migraine is more prevalent in females than males with a ratio of 3:1. It is primarily a complex neurovascular disorder involving local vasodilation of intracranial, extracerebral blood vessels and simultaneous stimulation of surrounding trigeminal sensory nervous pain pathway that results in headache. The activation of ‘trigeminovascular system’ causes release of various vasodilators, especially calcitonin gene-related peptide (CGRP) that induces pain response. At the same time, decreased levels of neurotransmitter, serotonin have been observed in migraineurs. Serotonin receptors have been found on the trigeminal nerve and cranial vessels and their agonists especially triptans prove effective in migraine treatment. It has been found that triptans act on trigeminovascular system and bring the elevated serum levels of key molecules like calcitonin gene related peptide (CGRP) to normal. Currently CGRP receptor antagonists, olcegepant and telcagepant are under consideration for antimigraine therapeutics. It has been observed that varying levels of ovarian hormones especially estrogen influence serotonin neurotransmission system and CGRP levels making women more predisposed to migraine attacks. This review provides comprehensive information about the role of serotonin and CGRP in migraine, specifically the menstrual migraine.

BackgroundThe prevalence of migraine is 3-folds higher in females than in males, and it is intricately related to the levels of estrogen. Estrogen may regulate the expression of metabolic enzymes and receptors of serotonin and also calcitonin gene-related peptide (CGRP), which are implicated in migraine pathogenesis.PurposeTo study the effects of estrogen on the components of serotonin system and CGRP in trigeminal ganglia of ovariectomized (OVX) rats.MethodsOVX rats were administered estrogen in silastic tubes and after 48 h, serum estrogen levels were determined. Trigeminal ganglia tissues were used for RT-PCRs of tryptophan hydroxylase (TPH), monoamine oxidase (MAO), serotonin receptors (5-HT1A, 5-HT1B, 5-HT2A), estrogen receptor (ER) and CGRP. Western blots of TPH and MAO were performed.ResultsEstradiol administration to OVX rats increased TPH mRNA levels, while decreased MAO mRNA levels in trigeminal ganglia tissue. Western blot data correlate with the gene expression results. The decreased mRNA levels of serotonin receptors following ovariectomy were restored in estrogen-replenished rats. The induced gene expression of ER in OVX rats was restored following estrogen replenishment.ConclusionEstrogen levels affect the levels of serotonin metabolizing enzymes and its receptors besides CGRP levels. Since TPH and MAO levels regulate circulating and physiologically available serotonin content, the regulation of serotonin metabolizing enzymes suggest a plausible mechanism by which estrogen alleviates migraine in women.