Pathophysiology of Migraine and Proposed Mechanisms of Action

Pathophysiology of Migraine and Proposed Mechanisms of Action of Acute Therapies

Objectives • Review the proposed pathophysiological mechanisms of migraine • Describe the proposed therapeutic targets for acute anti-migraine agents

Migraine in the New Millennium

CNS Activation During Migraine Copyright Permission Obtained Weiller, C, May, A, Limmroth, V, Nature Medicine 1995; 1(7): 658 -660, [http: //www. nature. com/nm] *Areas of red indicate cerebral blood flow increases (P <0. 001)

Capsaicin-Induced Cranial Pain Venous Sinus (May et al. 1998)

Trigeminovascular Migraine Pain Pathways (Adapted from Hargreaves, Shepheard 1999)

Acute Anti-migraine Targets (Adapted from Hargreaves, Shepheard 1999)

Vascular Mechanism of Action (Adapted from Hargreaves, Shepheard 1999)

5 -HT 1 B/1 D Receptor Immunoreactivity in Human Cranial and Coronary Arteries (Longmore et al. 1998)

Higher 5 -HT 1 B Receptor Expression in Human Meningeal vs Coronary Arteries (Longmore et al. 1998)

Neurogenic Mechanism of Action (Adapted from Hargreaves, Shepheard 1999)

Neurogenic Mechanism of Action • Neurogenic blood vessel vasodilation: Intravital microscopy in rat migraine model • 5 -HT 1 B/1 D agonists block release of vasoactive neuropeptides (CRGP) (Shepheard et al. 1999)

Human trigeminal Tract: CGRP Fibers Co-express 5 -HT 1 D Receptors

Neurotransmitter Systems in Primary Headache (Adapted from Edvinsson, Goadsby 1998)

Plasma Neuropeptides and Headache *Normalized concomitant with pain relief after sumatriptan (Edvinsson, Goadsby 1998)

Central Mechanism of Action (Adapted from Hargreaves, Shepheard 1999)

Human Dural Trigeminal Nerve and TNC: 5 -HT 1 D Immunoreactivity