Migraine (Midterm II) Flashcards
migraine
- leading cause of disability worldwide, esp in those under 50
- a primary headache disorder characterized by recurring pulsating headaches that are moderate to severe and last 2-72 hrs
- impart a sensitivity to normal sensory input (light, sound, head movement) as well as possibly nausea and vomiting
migraine aura
- about 20% of times, migraine is immediately preceded by aura (visual disturbances consisting of flashing lights or zigzag lines moving across the field of vision)
- thought to be driven by cortical spreading depression (a wave of neuronal depolarization that moved posterior to anterior across the cortex, and is followed by desensitization (depression))
migraine epidemiology
- risk seems to stem from a mix of genetic and environmental factors
- affects women more than men, and increased incidence in women begins after puberty, often ceasing with menopause; possible link to sex hormones
- some genetic contribution (for example, familial hemiplegic migraines)
familial hemiplegic migraine
- a very specific type of migraine due to genetic variations in a specific type of channel or gene that include weakness in half the body
- has autosomal dominant pattern of inheritance (you only need one allele of the affected gene to show symptoms, so family prevalence is high)
- associated with three known genetic mutations, for the P/Q-type Ca channel, the Na/K ATPase, and the Na channel subunit (recognize that these affect fundamental ions controlling neuronal excitability, so messing with motility will impact that)
- these mutations lower the threshold for cortical spreading depression (neurons are more excitable)
trigeminal system
- the trigeminal nerve is the largest of 12 cranial nerves that innervate the head/neck region
- its peripheral processes are divided into 3 branches (opthalamic, maxillary, mandibular) which serve 3 purposes (sensory afferents to sense pain and temp in the head region, innervation of the dura mater (membrane surrounding the brain) and controlling the cerebral blood vessels via the trigeminovascular system (v important in migraine))
migraine mechanism
- head pain is detected by the opthalmic branch of the trigeminal nerve in the dura mater and associated blood vessels
- cause still unknown, but thought to be a neurovascular disease (interaction btw neurons and vasculature in the head region) bc :
- cranial vasodilation creates headache -extracerebral vessels dilate during migraine attack
- vasoconstrictive drugs alleviate pain
5HT and migraine
- activation of and release of 5HT leads to vasoconstriction
- has been noted that migraneurs have v low 5HT lvls between attacks, and there seems to be a compensatory release when migraines happen
CGRP and migraine
- calcitonin gene-related peptide (CGRP) is located in the trigeminal peripheral afferents which detect sensation
- most of out nociceptors express it, and it’s released into the skin following activation, leading to dilation of surrounding vessels and the characteristic swelling as’d with pain
- CGRP seems to be elevated in those with migraine, suggesting a perturbation in the system
prophylactic treatments
taken daily to prevent attacks
abortive treatments
taken once an attack occurs to help alleviate pain and dispel symptoms faster
prophylactic migraine treatment
non-pharmaco: identifying and reducing triggers (diet, exercise, consistent sleep, avoiding excessive caffeine/alcohol, minimizing stress)
pharmaco: beta blockers like propranolol to decrease BP, anticonvulsants like gabapentin to block pain transmission (by blocking ca signaling), and antidepressants like amitriptyline (an SSRI) (if we can normalize circulating lvls of 5TH in migraineurs, maybe we can reduce frequency of attacks)
- generally only used for severe cases (the indv has migraines several times/month)
abortive migraine treatment
- non-specific analgesics (aspirin, aceptominophen, NSAID, opioids)
- risk of medication overuse headache (they get worse over time with use of these medications; persistent, prolonged use of analgesics w/o improvement)
caffeine and migrane
-caffeine is an adenosine receptor antagonist that leads to some vasoconstriction; it may block some of the vasodilation as’d with migraine, and also seems to increase absorption of some analgesics (acetominophen, ergotamines) which might improve migraine treatment during the attack, but in some may also trigger headaches or result in withdrawal rebound headaches
ergotamines for migraine treatment
- like LSD, these are ergot alkaloids derived from fungus on rye, but these have little binding at 5HT2A, hence no hallucinogenic effects
- they were the first specific anti-migraine agents, but are no longer first line therapy
- their affinity for 5HT1b/d receptors on the vasculature inhibits neurogenic inflammation by controlling constriction and dilation BUT low degree of receptor selectivity increases risk of experiencing drug-induced side effects
ergotamine side effects
- coronary vasoconstriction, often with associated ischaemic changes and anginal pain in patients with coronary artery disease, and in worst cases can lead to heart attack
- contraindicated in patients with peripheral vascular disease, coronary heart disease, uncontrolled hypertension and stroke
