Abstract
BackgroundMigraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund’s adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage.MethodsIn order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [51Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum.ResultsWe observed that [51Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [51Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants.ConclusionsWith these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system.Electronic supplementary materialThe online version of this article (doi:10.1186/s10194-015-0575-8) contains supplementary material, which is available to authorized users.
Highlights
Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population
Photo microscopy We were interested in observing whether the addition of inflammatory soup (IS) or complete Freund’s adjuvant (CFA) in our model had any direct effect at the place of addition on the dura mater, using photo microscopy
It is worth pointing out that removal of the bone for the direct application on the dura, reduces the possible changes that can be observed in meningeal vasculature. 15 min after the addition of IS (Fig. 1a/b) and CFA (Fig. 1c/d) we did not observe any changes in the meningeal vasculature
Summary
Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. Many researchers consider migraine to be a Several drugs have been shown to reduce migraine symptoms, or elicits migraine-like attacks [3] Studies, both in man and in experimental animals, have revealed anti-migraine effects of triptans, gepants (calcitonin gene-related peptide (CGRP) antagonists) and CGRP antibodies [4,5,6,7]. The published figures on BBB passage are in the vicinity of 3 % when given at clinically effective doses of triptans/gepants [5, 9,10,11] While these molecules have a small size, the CGRP antibodies will not likely cross the BBB at all and unlikely to antagonize receptor sites within the CNS [5]
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