Neurochemical disorders in migraine
A wide range of neurotransmitters is involved in the pathogenesis of migraine. The mechanism of action of drugs that effectively stop and prevent headaches is associated with effects on neurotransmitters, mainly serotonin.
According to preliminary clinical studies, the new calcitonin receptor antagonist of the gene-related peptide (CGRP) (MK-0974) and Rizatriptan® [Maxalt (Maxalf)] are highly effective. It is believed that in the future these medicines will constitute a new class of effective migraine treatment drugs.
Due to the fact that the antagonists of the CRP receptors do not have a direct vasoconstrictor action, this class of drugs may be an alternative for patients who have contraindications from the cardiovascular system to the use of triptans or if they are insufficiently effective.
Neurotransmitters involved in the pathogenesis of migraine:
– Serotonin (5-NT)
– GABA
– OCD
– Norepinephrine
– Dopamine
– Nitrogen oxide
– Estrogens
– Endorphins / Enkephalins
Serotonin is the most studied among the neurotransmitters involved in the development of migraine. The mechanism of action of many drugs used in the treatment of migraine, is associated with the modulation of serotonin activity. Drugs used to relieve headaches are aimed at activating the presynaptic, 5-HT1 inhibitory receptors of the dorsal nucleus of the suture.
Prophylactic drugs act as antagonists of postsynaptic excitatory 5-HT2 receptors. Some antidepressants block the reuptake of serotonin after it is released into the synaptic cleft, permanently reducing the activity of the receptors of the postsynaptic membrane. Some drugs, such as methysergide, act as a 5-HT1 or 5-HT2 receptor agonist.
Another important vasodilator neurotransmitter is nitric oxide. It activates the matrix metalloprotease (MMP), affecting brain development and the functioning of the blood-brain barrier (BBB). The spreading cortical depression in the initial phase is associated with an increase in the activity of MMP-9, which causes a violation of the BBB permeability and the phenomenon of plasma extravasation.
These effects explain how drugs and neurotransmitters that are outside the BBB act on the central nervous system during migraine. Moreover, changes in cerebral metabolism associated with MMP activity may explain the emergence of nonspecific changes in brain white matter in magnetic resonance imaging in 30% of migraine patients.
Sex hormones, especially estrogens, also have a significant effect on the course of migraine. Sex hormones are also called neurosteroids, which emphasizes their importance in neuroregulation. Estrogens are an important modulator of pain, which has a direct effect on pain sensitivity in the central nervous system.
Thus, the intracellular estrogen receptors are found in most of the enkephalin-producing neurons of the superficial lamina of the posterior horns of the spinal cord and the trigeminal nerve. The production of estrogen by these neurons enhances the production of enkephalin in 68% of patients. Estradiol also increases the levels of various painful neurotransmitters, such as 5-NT, GABA and endorphin.