Background and purpose The origin of
migraine pain is still elusive, but increasingly researchers focus on the
neuropeptides in the perivascular space of cranial vessels as important mediators of nociceptive input during
migraine attacks. The parasympathetic
neurotransmitters, pituitary
adenylate cyclase activating peptide-38 (
PACAP38) and
vasoactive intestinal peptide (VIP) may be released from parasympathetic fibres and activate sensory nerve fibres during
migraine attacks.
Triptans are effective and well tolerated in acute
migraine management but the exact mechanism of action is still debated.
Triptans might reduce circulating
neuropeptides. To examine this question, we examined the effect of
sumatriptan on VIP and
PACAP levels in vivo, under conditions without trigeminovascular system activation. Methods In 16 healthy volunteers we measured VIP and
PACAP levels before and after administration of subcutaneous
sumatriptan. We simultaneously collected blood samples from the internal and external jugular, the cubital veins and the radial artery, thereby covering both the cerebral and systemic circulation. VIP and
PACAP determinations were assayed blindly with respect to timing and vascular compartments, but with all samples of a patient in the same assay, to minimize the influence of interassay variation. Results We found no difference in VIP and
PACAP concentrations between the internal and external jugular, the cubital veins and the radial artery, (P>0.05), and the circulating levels of VIP and
PACAP did not change over time (P>0.05). We found excellent agreement between
neuropeptide levels in the internal and the external jugular system. Conclusion
Sumatriptan did not change the levels of circulating VIP and
PACAP in the intra or extra cerebral circulation in healthy volunteers. Under baseline conditions, without trigeminovascular activation,
sumatriptan does not affect the release of
neuropeptides VIP and
PACAP. Implications Our results indicate no effect of 5-HT1B/D receptor activation on circulating levels of VIP and
PACAP in humans without trigeminovascular activation. Given that
neuropeptides play an important role for
migraine it would be interesting to conduct a similar study in a
migraine population.