http://repub.eur.nl/res/aut/15121/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/16168/ 2003-11-26T00:00:00Z The term migraine stems from hemicrania, describing a periodic disorder consisting of paroxysmal unilateral headache, accompanied by nausea, vomiting, photophobia and/or phonophobia. Hemicrania was later changed to Latin words - hemigranea and migranea; eventually the French cognate, migraine, gained acceptance in the eighteenth century and has prevailed ever since. A working definition of migraine is benign recurring headache and/or neurological dysfunction usually attended by pain-free interludes and often provoked by stereotyped stimuli (1). Migraine may be triggered by certain factors (red wine, menses, hunger, lack of sleep, glare, perfumes, periods of let down) and relieved by others (sleep, pregnancy). Premonitory symptoms occur hours to a day or two before a migraine attack with or without aura. Migraine is more common in females, with a hereditary predisposition towards attacks and the cranial circulatory phenomenon appears to be secondary to a primary central nervous system (CNS) disorder. The Headache Classification Committee of the International Headache Society (IHS) published the classification and diagnostic criteria for headache disorders in 1988 (Table 1.1) (2). The terms “common migraine” and “classical migraine” have been replaced by “migraine without aura” and “migraine with aura”, respectively. These operational criteria have been validated by different approaches and have enabled us to distinguish different headache entities in a reliable manner (3-6). In recent years, the IHS criteria have been used world-wide in several multicentre double-blind drug trials, which have shown a reasonably consistent response rate to triptans (7), reflecting a consensus in the defined migraine group. In a recent MAZE survey, the Migraine Disability Assessment Scale (MIDAS) questionnaire has been used to assess the impact of migraine on work, home and social lives. MIDAS scores confirmed the debilitating effect of migraine; >50% of respondents had a MIDAS grade of III or IV, indicating moderate or severe disability. Less than one-third of patients reported that their current medication was consistently effective and only 36% were 'very satisfied' with their current therapy (8). These results show that migraine patients world-wide are still not receiving adequate treatment and a significant unmet need in migraine care still remains. http://repub.eur.nl/res/pub/13200/ 2003-09-01T00:00:00Z 1. Calcitonin gene-related peptide (CGRP), a potent vasodilator released from capsaicin-sensitive trigeminal sensory nerves, seems to be involved in the pathogenesis of migraine. Hence, CGRP receptor antagonists may serve as a novel treatment for migraine. This study was therefore designed to investigate the effects of BIBN4096BS (100, 300 and 1000 microg kg-1, i.v.), a potent and selective CGRP receptor antagonist, on capsaicin-induced carotid haemodynamic changes in anaesthetised pigs. Both vagosympathetic trunks were cut and phenylephrine was infused into the carotid artery (i.c.) to support carotid vascular tone. 2. Infusions of capsaicin (0.3, 1, 3 and 10 microg kg-1 min-1, i.c.) did not alter the heart rate, but dose-dependently increased the mean arterial blood pressure. This moderate hypertensive effect was not modified by BIBN4096BS. 3. Capsaicin infusion (10 microg kg-1 min-1, i.c.) increased total carotid, arteriovenous anastomotic and tissue blood flows and conductances as well as carotid pulsations, but decreased the difference between arterial and jugular venous oxygen saturations. These responses to capsaicin were dose-dependently blocked by BIBN4096BS. 4. Capsaicin infusion (10 microg kg-1 min-1, i.c.) more than doubled the jugular venous plasma concentration of CGRP. This effect was not blocked, but rather increased, by BIBN4096BS. 5. The above results show that BIBN4096BS behaves as a potent antagonist of capsaicin-induced carotid haemodynamic changes that are mediated via the release of CGRP. Therefore, this compound may prove effective in the treatment of migraine.