Topiramate inhibits trigeminovascular activation: an intravital microscopy study.

Br J Pharmacol. 2005 Sep;146(1):7-14.
Links
Topiramate inhibits trigeminovascular activation: an intravital microscopy study.
Akerman S, Goadsby PJ.
Headache Group, Institute of Neurology, London, UK.
Activation, or the altered perception of activation, of trigeminal nerves that innervate the cranial vasculature is considered to be a pivotal component of the pathophysiology of acute migraine. Calcitonin gene-related peptide (CGRP) levels are increased during migraine and after trigeminal nerve stimulation in the cat. Both CGRP and nitric oxide (NO) infusion causes headache and delayed migraine in migraineurs. Neurogenic stimulation of a cranial window, CGRP and NO injection all cause meningeal artery dilation in the rat when viewed using intravital microscopy. Topiramate is an antiepileptic drug with established efficacy as a migraine preventive, and has recently been shown to inhibit neurons of the trigeminocervical complex after superior sagittal sinus stimulation. In this study, we used intravital microscopy with neurogenic dural vasodilation, and CGRP- and NO-induced dilation to examine whether intravenous topiramate has effects on the trigeminovascular system. Topiramate was able to attentuate neurogenic dural vasodilation maximally after 15 min by 52% at 30 mg kg(-1) (t(5) = 6.78, n = 6); there was no significant inhibition at 10 mg kg(-1). There was also significant attenuation of the NO-induced dilation maximally after 15 min, at both 10 and 30 mg kg(-1) by 21% (t(6) = 6.09, n = 7) and 41% (t(6) = 5.3, n = 7), respectively. CGRP-induced dilation was not inhibited at either dose of topiramate.The study demonstrates that topiramate is likely to inhibit neurogenic dural vasodilation by inhibiting the release of CGRP from prejunctional trigeminal neurons, thus attenuating the dural vasodilation. Topiramate is not able to act postsynaptically at the blood vessels themselves as the CGRP-induced dilation was not attenuated. The data are consistent with an effect of topiramate on trigeminovascular activation which may form part of its preventive antimigraine mechanisms of action.
PMID: 15980877 [PubMed - indexed for MEDLINE]
PMCID: PMC1576242
Related articles
Orexin 1 receptor activation attenuates neurogenic dural vasodilation in an animal model of trigeminovascular nociception.
J Pharmacol Exp Ther. 2005 Dec; 315(3):1380-5. Epub 2005 Sep 13.
[J Pharmacol Exp Ther. 2005]
Nitric oxide synthase inhibitors can antagonize neurogenic and calcitonin gene-related peptide induced dilation of dural meningeal vessels.
Br J Pharmacol. 2002 Sep; 137(1):62-8.
[Br J Pharmacol. 2002]
Vanilloid type 1 receptors (VR1) on trigeminal sensory nerve fibres play a minor role in neurogenic dural vasodilatation, and are involved in capsaicin-induced dural dilation.
Br J Pharmacol. 2003 Oct; 140(4):718-24.
[Br J Pharmacol. 2003]
ReviewNeurogenic inflammation in the context of migraine.
Microsc Res Tech. 2001 May 1; 53(3):167-78.
[Microsc Res Tech. 2001]
ReviewThe trigemino-vascular system and migraine.
Pathol Biol (Paris). 1992 Apr; 40(4):313-7.
[Pathol Biol (Paris). 1992]
» See reviews... » See all...
Patient Drug Information
Topiramate (Topamax®)
Topiramate is used alone or with other medications to treat certain types of seizures in people who have epilepsy. Topiramate is also used with other medications to control seizures in people who have Lennox-Gastaut synd...
Source: AHFS Consumer Medication Information