The role of CGRP and nicotinic receptors in centrally evoked facial blood flow changes.
The release of CGRP in humans is associated with the occurrence of migraine headaches. The vasoactive neuropeptide is released by afferent neurones originating in the peripherally located trigeminal ganglion supplying the dura mater. The role of CGRP in migraine is further supported by recently released data showing that the CGRP-antagonist BIBN4096BS is clinically effective for the treatment of migraine headaches. Yet, the trigger for CGRP release during migraine attacks is not identified. It is suggested that the peripheral CGRP release during a migraine attack might be either triggered by direct activation of afferent dural neurones, or, by indirect activation via the central nervous system. Recently, we were able to show that the CGRP-antagonist BIBN4096BS is able to inhibit vasodilation induced by trigeminal ganglion stimulation. Now, we extend our studies to the investigation of facial blood flow changes induced by electrical stimulation of the brainstem trigeminal nucleus caudalis (TNC). Here, we show that stimulation of the TNC leads to a pronounced increase of facial blood flow. The nicotinic antagonist Hexamethonium reduced the evoked flow by approximately 50% (30 mg/kg), while the muscarinic antagonist Atropin did not influence the stimulation evoked blood flow. Application of BIBN4096BS (0.3 mg/kg, i.v.) diminished the evoked flow almost completely. Therefore, we conclude that CGRP represents the key player in TNC-induced facial vasodilation, while activation of nicotinic receptors modulates centrally induced peripheral neurogenic vasodilation.
Just
Stefan
S
CNS Research, Boehringer Ingelheim Pharma KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany. stefan.just@bc.boehringer-ingelheim.de
Arndt
Kirsten
K
Doods
Henri
H
D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D005145:Face / Q000098:blood supply / Q000294:innervation* / Q000502:physiology*; D008297:Male; D008881:Migraine Disorders / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014278:Trigeminal Nuclei / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D011978:Receptors, Nicotinic; D015740:Calcitonin Gene-Related Peptide