migraine and emesis

• Migraine is a painful, pulsing headache typically lasting 4 hours to 3 days, often unilateral and associated with photophobia and phonophobia.
• About 7% of men and 17% of women have experienced at least one migraine in a year.
• Migraine can be divided into migraine with and without aura.
• Aura is an initial visual disturbance, around 30 minutes, where the visual area is lost and the surrounding area 'shimmers'.
• Unilateral throbbing headache, lasting 4 to 72 hours, is a common symptom of migraine.
• Nausea and Vomiting are common in 85% of migraine sufferers.
• Resolution of migraine usually occurs during deep sleep and loss of headache.
• Genetics plays a significant role in migraine, with studies showing that 42% of migraine is heritable.
• A genome-wide association meta-analysis identified 38 genomic loci that affect migraine risk.
• The relative risk of migraine without aura is 1.9 in first degree relatives of probands with migraine without aura.
• The relative risk of migraine with aura is 3.8 in first degree relatives of probands with migraine with aura.
• Genetic biomarkers for monogenic subtypes of migraine or migraine-related syndromes include Familial hemiplegic migraine, Type 1 (CACNA1A gene), Type 2 (ATP1A2 gene), and Type 3 (SCN1A gene).
• Neurones in the Opthalmic Division of the Trigeminal Nerve contain Calcitonin gene related peptide (CGRP), a potent vasodilator and plasma CGRP increases in migraine.
• Pain in the Bipolar Trigeminal Nerve: pain in the bipolar trigeminal nerve is likely caused by activation of the trigeminovascular system (TGVS).
• Vasodilation and migraine: the role of vasodilation in migraine is hotly debated as conflicting findings of imaging studies of meningeal and cortical vessels in humans during migraine attack, vasodilation not seen with spontaneous migraine.
• Aura: wave of electrical activity starting in the occipital cortex and spreading slowly at 2 - 3 mm/min associated with visual hallucinations across the visual field that is reproducible in the same individual.
• Bipolar Trigeminal Nerve: the bipolar trigeminal nerve connects the dorsal horn of the spinal cord with the meninges and cranial blood vessels.
• Therapy that prevents the aura can still leave the headache.
• Migraine Pain: Trigeminal nerve, which has three divisions that innervate the forehead and eye (ophthalmic V1), cheek (maxillary V2) and lower face and jaw (mandibular V3), is activated by facial touch, pain and temperature.
• Opthalmic Division of the Trigeminal Nerve: the opthalmic division of the trigeminal nerve innervates the frontal and parietal cortex and meninges vascular beds.
• Trigeminal Neuralgia: Trigeminal nerve nerves project to trigeminal nucleus caudalis neurones, onwards to thalamus and cortex.
• Mutations in CACNA1A gene that encodes the pore-forming α1A subunit of the P/Q voltage-gated calcium channel (chromosome 19) cause 50% cases of Familial hemiplegic migraine.
• Mutations in ATP1A2 gene that encodes the Na+/K+ pump α2 subunit cause 30% of patients with Familial hemiplegic migraine.
• Mutation in TRESK K2P potassium channel in spinal neurons associated with common migraine.
• SCN1A (sodium voltage-gated channel alpha subunit 1) encodes NaV1.1.
• The original theory of migraine was Vascular Origin (Wolff 1940’s).
• Migraine involves interactions with higher centres and is partly a learned or associative response.
• A combination of anti-emetics and mild sedation (benzodiazepine) can be used to reduce severe nausea.
• Corticosteroids are not very effective for control of acute vomiting, and 5HT 3 antagonists are not very effective against non-chemotherapy vomiting.
• Imaging studies and experimental studies have highlighted the complexities of underlying mechanisms of migraine.
• Transient neurologic symptoms (aura) which is likely caused by cortical spreading depression (CSD) slowly propagating cortical waves of neuronal and glial cell depolarisation, start in the visual cortex and are followed by long-lasting (>1 hour) depression of activity.
• Most evidence for CSD is from animal models but indirect evidence from fMRI studies in humans.
• The relationship between aura and pain in migraine is unclear.
• CGRP increases in the cortex and a modulatory effect of CGRP upon CSD (calcium-sensitive dye) is observed.
• CGRP (calcitonin gene-related peptide) is released during a migraine attack and IV injection of CGRP provokes a migraine attack in migraine patients.
• Vomiting is a coordinated involuntary reflex involving powerful sustained contraction of the abdominal chest wall and diaphragm muscles, rapid evacuation of stomach contents up to and out of the mouth, and suspension of breathing.
• Pain relief in episodic and chronic migraine is observed with anti-CGRP therapies.
• Dural application of CGRP causes vasodilation but not nociceptor activation.
• Headache is a common symptom of COVID-19 infection, affecting 10-70% of patients and presenting with migraine-like features in 25%.
• CGRP is expressed in the C-fibres and receptor expressed by Ad-fibres in the trigeminal ganglia, which is central to the trigeminovascular reflex, triggered during migraine and leading to perception of pain.