During activation of trigeminal sensory fibers surrounding cerebral and meningeal blood vessels, the stimulated nerve fibers release a variety of inflammatory and vasodilatory neuroactive substances, such as calcitonin gene related peptide (CGRP), substance P, NO, and cytokines.1,2 References 1. Bolay H., Reuter U, Dunn AK, et al. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nature Medicine. 2001;8(2):136-142. 2. Williamson DJ, Hargreaves RJ. Neurogenic inflammation in the context of migraine. Microsc Res Tech. 2001;53(3):167-78.
• Characterised by episodic headache, typically
unilateral, associated with vomiting and visual
• Headache may be bitemporal and generalised
without focal visual or neurological
The Headache Dilemma…
HOW COMMON IS MIGRAINE
World- 15-20% of women
10-15% of men
In India 15-20% migraine
Adults-female: male ratio is 2:1
In childhood boys and girls are
affected equally until puberty when
predominance shifts to girls
• ↓ cerebral blood flow at the onset of an attack in migraine
with aura. During phase of attack, dilatation of extracranial
arteries related to fluctuations in blood 5-ht levels.
• Genetic predisposition.
• Chocolate, cheese, alcohol may precipitate attack.
• Episodes ↑ perimenstrually, at weekends or in women
taking oral contraceptives.
• Stress & anxiety may initiate an attack.
Release of CGRP, substance P &
Vascular theoryo Intracerebral blood vessel constriction –
o Intracranial/extra cranial blood vessel
Serotonin theoryo Decreased 5-ht levels linked with migraine
o Specific 5-ht receptors found in blood
vessels of brain
Chemicals in the
brain cause blood
vessel dilation and
inflammation of the
Changes in nerve
cell activity and
may result in visual
spread to other
regions of the brain.
Migraine originates deep
within the brain
irritates the trigeminal
nerve, resulting in
severe or throbbing
o Migraine with aura
o Migraine without aura
o Complicated migraine
PHASES OF ACUTE
o Vague premonitory symptoms that
begin from 12 to 36 hrs before the aura
o Symptoms include: Yawning
Craving or distaste for various foods
o Duration- 15-20min
o Aura is a warning or signal before onset of
o Symptoms include
Flashing of lights
Zig zag lines
Difficulty in focussing
o Duration:15-30 min
o Headache is generally unilateral and
is associated with symptoms like:
o Duration:4-72 hrs
Following headache, patient
o Severe exhaustion
o Some patients feel unusually fresh
o Duration: few hrs to 2 days
Starts after puberty, continues till late midlife.
Attack may occur from a few days to several months.
Attacks may last for hours to days.
Premonitory symptoms – zig-zag lines, flashing, coloured lights,
defects in visual field & dysphasias with headache.
Headache localized to frontal region & spreads to whole of one
side of head – pain severe & throbbing associated with vomiting,
Patient is shifted to a bed in darkened room.
Non pharmacological treatment
o Identification of triggers
o Relax techniques
o Abortive treatment
o Preventive treatment
Non specific treatmento Aspirin
Specific treatmentErgot alkaloids:-ergotamine
Antinauseant drugs:- metaclopramide
Triptans work best in 1st couple of hrs of attack
Ergotamine works at any time during the attack
Avoid dietary and other precipitants.
Maintain a diary of attacks.
Stop oral contraceptives.
Soluble Aspirin (600-900 mg) or Paracetamol (1 Gm) with or
without Metoclopramide as antiemetic.
Ergotamine tartarate, 0.5-1.0 mg sublingually may abort
headache if taken as soon as visual symptoms are felt. No More
than 12 mg in a week. Excessive use may lead to vasospasm &
paradoxical headache. Contraindicated in pregnancy, IHD &
peripheral vascular disorders.
• Serotonin agonist-triptans – Sumatriptan for acute attacks of
migraine (100 mg). No more than 300 mg per 24 hours or Inj.
Sumatriptan 6 mg SC. Not more than 2 injections per 24
hours. Highly efficacious.
• Prophylaxis if attacks occur weekly:
Propranolol : 40-80 mg 8 hrly.
: 1.5-3 mg at night.
: 25-100 mg at night.
Migraine & Oral Contraceptives
C/I migraine if there is typical aura, focal
features or if it is severe and lasts for
more than 72 hrs despite treatment
Acute Migraine Attack
• It appears to begin in serotonergic (5-HT) and
noradrenergic neurons in the brain. These
monoamines affect cerebral & extracerebral
vasculature and cause release of vasoactive
substances such as H, PGs, neuropeptides
involved in pain, i.e. neurogenic inflammation
can be inhibited by antimigraine drugs.
• Migraine aura of visual or sensory disturbance
originates in occipital or sensory cortex.
• Throbbing headache is due to dilatation of
vessels – sensitive arteries outside the brain.
Treatment – Stepped Approach
• Aspirin 600 mg oral dispersible (soluble) as
early as possible.
• Alternatives are Paracetamol, Ibuprofen,
• Metoclopramide or Domperidone (dopamine
agonists) – antiemetics that promote gastric
emptying & enhance absorption of analgesic.
• Efficient use of analgesic & antiemetic is
adequate for majority of attacks.
Severe migraine attacks should be treated with
triptans – Sumatriptan. Headache may return in
6-36h in 1/3rd patients. Use second dose.
Ergotamine 1-2 mg used if other treatments
failed, but not within 12h of the last dose.
Do not give triptans until 24h have elapsed after
Sumatriptan – C/I
Prophylaxis of migraine
Within 2 wks after stopping MAOIs
• C/I: HT, IHD, Prinzmetal’s angina, Lactation,
Within 2 wks of MAOIs, Within 24 hrs of
treatment with another 5-HT agonist or
Tab. Rizact 5 mg
Partial agonist at α-adrenoceptors
Partial agonist at serotonergic receptors.
Constricts all peripheral arteries.
Effect persists for 24h, repeated doses cause
Tablets 1 mg crushed before swallowing.
Initially 1-2 mg, maximum 4 mg in 24h.
Not more than 8 tablets in a week.
Rectal suppositories of 2 mg preferred.