The blood-brain barrier in migraine treatment.
Salient aspects of the anatomy and function of the blood-barrier barrier (BBB) are reviewed in relation to migraine pathophysiology and treatment. The main function of the BBB is to limit the access of circulating substances to the neuropile. Smaller lipophilic substances have some access to the central nervous system by diffusion, whereas other substances can cross the BBB by carrier-mediated influx transport, receptor-mediated transcytosis and absorptive-mediated transcytosis. Studies of drugs relevant to migraine pathophysiology and treatment have been examined with the pressurized arteriography method. The drugs, given both luminally and abluminally, provide important notions regarding antimigraine site of action, probably abluminal to the BBB. The problems with the BBB in animal models designed to study the pathophysiology, acute treatment models and preventive treatments are discussed with special emphasize on the triptans and calcitonin gene-related peptide (CGRP). The human experimental headache model, especially the use of glycerol trinitrate (the nitric oxide model), and experiences with CGRP administrations utilize the systemic administration of the agonists with effects on other vascular beds also. We discuss how this can be related to genuine migraine attacks. Our view is that there exists no clear proof of breakdown or leakage of the BBB during migraine attacks, and that antimigraine drugs need to pass the BBB for efficacy.
Edvinsson
L
L
Department of Internal Medicine, University Hospital, Lund, Sweden. lars.edvinsson@med.lu.se
Tfelt-Hansen
P
P
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000503:physiopathology; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008959:Models, Neurological; D014363:Tryptamines / Q000008:administration & dosage / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
D014363:Tryptamines; D014665:Vasodilator Agents; D015740:Calcitonin Gene-Related Peptide