Investigations of pituitary adenylate cyclase-activating polypeptide isoforms in a human experimental model of headache (2020)


Migraine is a common, multifactorial neurological disorder, exhibiting an intricate pattern of heterogeneity, as shown by its different clinical manifestation, and treatment variability. Despite the substantial advance in migraine research and novel emerging therapies, signaling pathways underlying migraine pathophysiology are yet to be elucidated, and better pharmacological treatments are warranted.
PACAP is a pleiotropic signaling neuropeptides implicated in migraine. The present thesis includes three studies that investigated the role of PACAP isoforms in migraine and headache, including its vascular components. 
I: Migraine without aura patients are hypersensitive to PACAP27 infusion. II: We found that PACAP27-induced headache and dilated extracerebral arteries and slightly constricted middle cerebral artery in healthy participants. Similarly, to the long-lasting effect of PACAP38 on extracerebral arteries, PACAP27 also caused sustained, and prolonged dilation of extracerebral arteries. III: We investigated the role of sumatriptan and ketorolac in human experimental model of headache using PACAP38 infusion. We found that pre-treatment with both drugs had no effect on PACAP38-induced headache. However, we found that post-treatment with ketorolac compared to sumatriptan was more effective in attenuating PACAP38-induced headache. 
In conclusion, PACAP27 is also able to provoke migraine and possess vasodilatory properties like PACAP38 with some physiological differences. 

Place of employment

PhD author

Date and place of defense

16th november, 2020, Rigshospitalet-Glostrup, Denmark 


Messoud Ashina, Prof, MD, PhD, DMSc (Primary supervisor)
Henrik BW Larsson, Prof, MD, DMSc (Co-supervisor)
Faisal Mohammad Amin, MD, PhD (Co-supervisor)
Nanna Arngrim, MD, PhD (Co-supervisor)



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