Intracisternal injection of inflammatory soup activates the trigeminal nerve system.
The release of calcitonin gene-related peptide (CGRP) and sensitization of the trigeminal nerve system are important elements in migraine pathophysiology. Sensitization can be induced by topical meningeal administration of inflammatory soup (IS). CGRP release is a marker of trigeminal nerve activation. We examined the effect of intracisternal IS administration on CGRP release in rat jugular vein blood at baseline, 2 and 15 min after the beginning of IS infusion. IS administration caused a significant increase of CGRP levels after 2 and 15 min compared with baseline. Daily oral treatment with topiramate for 4 and 8 weeks led to a dose- and time-dependent reduction of IS-induced CGRP release. Sumatriptan also attenuated stimulated neuropeptide release. These results indicate that intracisternal IS administration leads to activation of the trigeminal system. The inhibition of CGRP release by topiramate offers a possible mechanism that may in part account for the preventative antimigraine activity of this drug.
Hoffmann
J
J
Charité-Universitätsmedizin Berlin, Department of Neurology, 10117 Berlin, Germany. jan.hoffmann@charite.de
Neeb
L
L
Israel
H
H
Dannenberg
F
F
Triebe
F
F
Dirnagl
U
U
Reuter
U
U
D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage; D015740:Calcitonin Gene-Related Peptide / Q000097:blood* / Q000187:drug effects; D015232:Dinoprostone / Q000008:administration & dosage; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006632:Histamine / Q000008:administration & dosage; D017442:Histamine Agonists / Q000008:administration & dosage; D007249:Inflammation / Q000139:chemically induced; D007276:Injections, Intraventricular; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010120:Oxytocics / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000008:administration & dosage; D018490:Serotonin Agents / Q000008:administration & dosage; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D000077236:Topiramate; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage
D017442:Histamine Agonists; D018696:Neuroprotective Agents; D010120:Oxytocics; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D014665:Vasodilator Agents; D000077236:Topiramate; D005632:Fructose; D012701:Serotonin; D006632:Histamine; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D001920:Bradykinin