PATHOPHYSIOLOGY OF MIGRAINE

DR MALLUM C.B

EXCITABLE BRAIN

• DRN- direct stimulation causes migraine.

Serotonin- central to forebrain. 5HT2- migraine.

5HT1 presynaptic- inhibits DRN, peripheral stimulation from circulating serotonin.

Unstable serotonergic system.Ergot- 5HT1 stimulator. Ergotamine- vasodilator. Triptans-5HT1D agonist.

• Descending analgesic pathway-

• PAG - Midbrain

PROF’S PATHOPHYSIOLOGY

• Prophylaxis – Inhibit 5HT2 in forebrain. egpropranolol.

• Providing serotonin eg amitryptiline for accumulation of serotonin at 5HT1.

• Tension headache – low level of serotonin.

• Moscowicz- AAN

• Goadsby.

• Genetic predisposition

• Menstrual- premenstrual migraine.

• Triggers that are repeatedly associated with an

Attack e g glare, loud noise, certain odors, certain foods (or delaying a meal), hormonal changes, head trauma, and NO.

premonitory symptoms irritable, have food cravings, or experience fatigue or excessive yawning.

CSD

• a migraine trigger• CSD occurs in the cerebral cortex, cerebellum,

and hippocampus.• Intracellular calcium rises• NO, arachidonic acid, protons (H+), and

potassium (K+) are released extracellularly.• Matrix metalloprotease affects the bloodbrain

barrier.• Speed 3mm/s, goes to occipital,• CSD causes aura.

CSD

• Meningeal nociceptors are activated.

• Mast cells are activated and degranulate.

• The trigeminovascular reflex is activated.

• Trigeminal neurons supplying the dural vessels release calcitonin gene-related peptide (CGRP), substance P, and neurokinin A.

• The vessels dilate and become inflamed, and plasma protein extravasation occurs (also known

as sterile neurogenic inflammation).

peripheral sensitization

• At this point, the first-order trigeminal neuron has been activated (peripheral sensitization) and carries pain signals centrally.

• The patient may experience pounding pain and pain with head movement.

• If treated during the early stages of an attack when only peripheral sensitization has occurred, the migraine may be terminated fully.

trigeminoparasympatheticreflex

• Through its polysynaptic connections with the SSN(superior salivatory nucleus)

• parasympathetic fibers innervating the duralvessels release acetylcholine, NO, and vasoactive intestinal polypeptide.

• Clinically, the patient may develop miosis, ptosis, a red eye, lacrimation, and nasal stuffiness or rhinorrhea.

central sensitization

• second- and third-order neurons may be activated (trigeminothalamic and thalamocortical).

• the phenomenon known as wind-up is involved.

• Glutamatergic and NO transmission are involved.

• The clinical manifestation of

• central sensitization is cutaneous allodynia.

central sensitization

• The patient may report scalp tenderness and facial, neck, or even extremity pain occurring spontaneously or in response to nonpainfulstimuli.

• Patients may even report that their hair hurts.• Once central sensitization has occurred, the

attack is much harder to treat, and triptan drugs, such as sumatriptan, may no longer work.

• However, nonsteroidal anti-inflammatory drugs• (NSAIDs) and dihydroergotamine may still be

effective.

central sensitization

• Central sensitization is more likely to occur as the duration of an attack increases and is also more likely to be present in chronic migraine

than episodic migraine.

Possible substrates for clinical features of migraine

• Pain – trigeminovascular system

- throbbing: pain producing innervation of large cranial vessels

- Unilateral: trigeminal nerve/nucleus.

• Nausea –Trigeminal connections with caudal medial NTS

• Light- Abnormal brain stem modulation of sensory input(locus coerulus)

ANATOMY OF MIGRAINE

Opthalmic division of the trigeminal nucleus –cerebral vessels,pial vessels, large venous sinuses, dura mater.

Upper cervical dorsal roots –posterior fossa

Neurons secrete substance P and CGRP

First order neuron- Trigeminal ganglion

Second order neuron- Trigeminal nucleus

(Quintothalamic tract) : Trigeminal nucleus caudalis& and C1-2 dorsal horns.

PHYSIOLOGY OF PERIPHERAL CONNECTIONS

• Plasma protein extravasation-

• Neuropeptide studies-CGRP & Substance P

PHYSIOLOGY OF CENTRAL CONNECTIONS

• The Trigeminocervical complex-

From nucleus caudalis to dorsal horn of high cervical cord.

These are second order neurons for intracranial pain producing structures.

• Higher order processing- Thalamus: Ventral posteromedial,medial nucleus of posterior complex,intralaminar thalamus, Ventrobasalcomplex

CENTRAL MODULATION

• Midbrain - Periaqueductal gray matter

• Hypothalamus -?

• Final - Cortex - Insulae , Frontal cortex , Anterior cingulate cortex ,Basal ganglia

RX

• Steroids as rescue medication in Chronic Daily Headache.