The online version of this article (doi:10.1186/1129-2377-15-7) contains supplementary material, which is available to authorized users.
The study received support by the Emerging Fields Initiative of the Friedrich-Alexander-University. The authors declare no conflict of interest.
CK performed the experiments and wrote the manuscript; the present work was performed to obtain the degree Dr. med.’ at the Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)’. BS-B sliced brainstems, KM wrote the manuscript and supervised the project. MJMF designed the study, analyzed the data and wrote the manuscript. All authors read and approved the final manuscript.
CGRP is contained in a substantial proportion of unmyelinated trigeminal neurons innervating intracranial tissues. Previously, we have described a hemisected rodent scull preparation and later the intact trigeminal ganglion to measure stimulated CGRP release from trigeminal afferents.
Here, we establish a preparation for examining CGRP release from central trigeminal terminals using single fresh slices of the mouse medullary brainstem.
Basal and stimulated amount of CGRP substantially exceeded the detection level. Experiments were designed as matched pairs of at least six brainstem slices per animal. Stimulation with high potassium induced calcium-dependent and reversible CGRP release. Capsaicin stimulation of TRPV1 provoked concentration-dependent CGRP release. The anti-migraine drug naratriptan did not inhibit capsaicin-induced CGRP release from peripheral terminals but inhibited the release from brainstem slices. The glutamate antagonist kynurenate showed a similar pattern of site-specific inhibition of CGRP release.
As observed earlier for other drugs used in the treatment of migraine this indicates that the central terminals in the spinal trigeminal nucleus may be the main site of action. The preparation allows evaluating the trigeminal brainstem as a pharmacological site of action.
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- Release of CGRP from mouse brainstem slices indicates central inhibitory effect of triptans and kynurenate
Barbara E Nixdorf-Bergweiler
Michael JM Fischer
- Springer Milan
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