Primary trigeminal afferents are the main source for stimulus-induced CGRP release into jugular vein blood and CSF.
BACKGROUND
Administration of inflammatory soup (IS) leads to a significant release of calcitonin gene-related peptide (CGRP). Whether IS-induced CGRP release originates in primary or secondary neurons of the trigeminovascular system has not been clarified.


METHODS
We determined CGRP release into the external jugular vein and in cerebrospinal fluid (CSF) following intracisternal IS administration using an in vivo rat model. We further performed polymerase chain reaction (PCR) and immunohistochemistry of the trigeminal ganglion and brainstem (trigeminal nucleus caudalis). To further elucidate a primary vs. secondary origin, experiments were repeated after neonatal capsaicin treatment (NCT) as this treatment destroys primary trigeminal afferents.


RESULTS
IS-induced CGRP release into the external jugular vein and CSF were significantly reduced after NCT in both compartments but inhibition was more pronounced in jugular vein blood than in CSF. Baseline CGRP levels were not affected by NCT. PCR results show that following NCT, CGRP mRNA was significantly reduced in the trigeminal ganglion but not in the brainstem. Immunohistochemistry of the TG and brainstem support these results.


CONCLUSIONS
We conclude that resting state CGRP levels can be maintained after trigeminal denervation of the meninges. However, for functional purposes primary trigeminal afferents are mandatory as they are the major source for stimulus-induced CGRP release.
Department of Neurology, Charité - Universitätsmedizin Berlin, Germany.
Jan
J
Hoffmann
Sascha
S
Wecker
Lars
L
Neeb
Ulrich
U
Dirnagl
Uwe
U
Reuter
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000235:genetics; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000494:pharmacology; D007601:Jugular Veins / Q000378:metabolism*; D008297:Male; D008881:Migraine Disorders / Q000378:metabolism*; D009443:Neuritis / Q000139:chemically induced / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000166:cytology / Q000378:metabolism*
D018836:Inflammation Mediators; D012333:RNA, Messenger; D018689:Sensory System Agents; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin