PCOL 8-1 Migraine and treatment

Migraine Characteristics

• The aura phase of migraine is characterized by symptoms such as zigzag lines, blurred vision, and blind spots.
• Migraine without aura is more common than migraine with aura.

Age of Onset and Origin

• The onset of migraine usually occurs during adolescence and early adulthood.
• Migraine is believed to originate from the dura mater, pia mater, and large cranial vessels.

Nerve Innervation

• The trigeminal nerves innervate the large cranial vessels, smaller meningeal vessels, meninges, trigeminal nucleus caudalis, and spinal cord trigeminocervical complex.

Neurotransmission

• C-fibers release the neurotransmitter calcitonin gene-related peptide (CGRP) in response to stimuli such as heat, pressure, and injury.
• The trigeminal ganglion plays a key role in transmitting pain signals to the brain in migraine.

Vasodilation and Pain Pathway

• Vasodilation of intracranial and meningeal blood vessels contributes to migraine pain.
• The pathway of pain sensation in migraine starts from the trigeminal ganglion, passes through the spinal tract and nucleus, and ends in the thalamus and cortex.

Receptors and Neurotransmitters

• The 5-HT1 receptor is inhibitory and coupled to Gi protein.
• Serotonin (5-HT) is a neurotransmitter implicated in migraine.
• 5-HT1D and 5-HT1F receptors are found on intracranial blood vessels in migraine.

Migraine Treatment

• NSAIDs (non-steroidal anti-inflammatory drugs) inhibit COX to prevent prostaglandin synthesis and are most effective when given early or right before a migraine attack.
• Ergotamines cause vasoconstriction, block trigeminal nerve transmission, and are contraindicated in cardiovascular disease.
• Triptans inhibit trigeminal nerve transmission peripherally and centrally, inhibit release of vasoactive peptides from meningeal blood vessels, and cause vasoconstriction via stimulation of 5-HT1B receptors.
• Different triptans differ mainly in the length of their half-lives and are agonists of 5-HT1B/1D/1F receptors.

Treatment Resistance and Side Effects

• The treatment resistance rate for migraine patients is approximately 30-40%.
• Anticonvulsants can cause weight gain as a side effect.
• Anticonvulsants and membrane stabilizers alter ion channel activity to reduce excitability of the cortex.
• Antidepressants increase the concentrations of 5-HT and NAd by inhibiting their transporters.
• 5-HT1F antagonists are currently being investigated as a potential new treatment for migraine.