Effects of sumatriptan on capsaicin-induced carotid haemodynamic changes and CGRP release in anaesthetized pigs.
It is suggested that during a migraine attack capsaicin-sensitive trigeminal sensory nerves release calcitonin gene related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Hence, inhibition of trigeminal CGRP release may prevent the above vasodilatation and, accordingly, abort migraine headache. Therefore, this study investigated the effects of sumatriptan (100 and 300 microg/kg, i.v.) on capsaicin-induced carotid haemodynamic changes and on CGRP release. Intracarotid (i.c.) infusions of capsaicin (10 microg/kg/min, i.c.) increased total carotid, arteriovenous anastomotic and capillary conductances as well as carotid pulsations, but decreased the difference between arterial and jugular venous oxygen saturations. Except for some attenuation of arteriovenous anastomotic changes, the capsaicin-induced responses were not affected by sumatriptan. Moreover, i.c. infusions of capsaicin (0.3, 1, 3 and 10 microg/kg/min, i.c.) dose-dependently increased the jugular venous plasma concentrations of CGRP, which also remained unaffected by sumatriptan. The above results support the contention that the therapeutic action of sumatriptan is mainly due to cranial vasoconstriction rather than trigeminal (CGRP release) inhibition.
Department of Pharmacology, Cardiovascular Research Institute 'COEUR', Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands.
U
U
Arulmani
J P C
JP
Heiligers
I M
IM
Garrelds
A
A
Sánchez-López
E W
EW
Willems
C M
CM
Villalón
P R
PR
Saxena
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000097:blood / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D002339:Carotid Arteries / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008881:Migraine Disorders / Q000188:drug therapy; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D034421:Sus scrofa; D014276:Trigeminal Nerve / Q000502:physiology; D014628:Vagotomy; D014664:Vasodilation / Q000502:physiology
D017366:Serotonin Receptor Agonists; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin