Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers.
The role of nitric oxide (NO) in migraine has been studied in the experimental glyceryl trinitrate (GTN)-infusion headache model. We hypothesized that GTN-induced headache may activate the trigeminovascular system and be associated with increased levels of sensory neuropeptides, including calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers received subcutaneous sumatriptan 6 mg or placebo. This was succeeded by 20 min of GTN (0.12 µg kg(-1) min(-1)) infusion. At baseline no subject reported headache (using verbal rating scale from 0 to 10) and the jugular CGRP-like immunoreactivity (-LI) level was 18.6 ± 2.5 pmol/l. After a 20-min intravenous infusion of GTN 0.12 µg kg(-1) min(-1), median peak headache intensity was 4 (range 2-6) (P < 0.05), while jugular CGRP-LI levels were unchanged (19.0 ± 2.8 pmol/l; P > 0.05). There were no changes in VIP-, NPY- or somatostatin-LI. In conclusion, the NO donor GTN appears not to induce headache via immediate CGRP release.
Kruuse
C
C
Danish Headache Centre, Glostrup Hospital and Glostrup Research Park, Copenhagen, Denmark.
Iversen
H K
HK
Jansen-Olesen
I
I
Edvinsson
L
L
Olesen
J
J
D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000097:blood*; D018592:Cross-Over Studies; D005260:Female; D006261:Headache / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D020030:Nitric Oxide Donors / Q000009:adverse effects*; D005996:Nitroglycerin / Q000009:adverse effects*; D012016:Reference Values; D013004:Somatostatin / Q000097:blood; D018170:Sumatriptan / Q000008:administration & dosage; D014660:Vasoactive Intestinal Peptide / Q000097:blood; D014662:Vasoconstrictor Agents / Q000008:administration & dosage
D009478:Neuropeptide Y; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D018170:Sumatriptan; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide