Serotonin and CGRP in Migraine

Abstract

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.

Baicalin Alleviates Nitroglycerin-induced Migraine in Rats via the Trigeminovascular System

“…Nitric oxide level was increased via exogenous or endogenous pathway and broke the NO‐ET balance. It may give rise to serum response and platelet aggregation by protein kinase C /extracellular signal‐regulated kinase (PKC‐ERK) pathway, which all contribute to migraine attacks (Aggarwal et al , ; Jha et al , ). Calcitonin gene‐related peptide level can also be elevated by cyclic 3′,5′‐guanosine monophosphate (cGMP) pathway so as to indirectly cause neuroinflammation and C‐fos gene activation (Levy et al , ).…”

Electroacupuncture Pretreatment at GB20 Exerts Antinociceptive Effects via Peripheral and Central Serotonin Mechanism in Conscious Migraine Rats

“…A low central 5-HT disposition is associated with an increase in the peripheral 5-HT release during a migraine attack, and this is the most convincing change of 5-HT metabolism in migraine [14, 38]. 5-HT interacts with different receptors on trigeminovascular pathway and regulates the nociceptive information.…”

Serotonin in Neurological Diseases

“…Triptans-the 5-HT1B/1D receptor agonists-are successfully used in migraine therapy. The medications that inhibit the reuptake of 5-HT (e.g., selective 5-HT reuptake inhibitor, SSRI) are efficient in chronic pain conditions among which are chronic headaches [31].…”