PACAP38 dose-response pilot study in migraine patients.

Area of Science:

• Neurology
• Neuroscience
• Pharmacology

Background:

• Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) at 10 pmol/kg/min is known to induce migraine-like attacks in patients with migraine without aura (MO).
• The potential of lower PACAP38 doses to elicit similar responses requires investigation.

Purpose of the Study:

• To investigate the migraine-inducing potential of lower doses of PACAP38 in patients with MO.
• To explore a dose-response relationship for PACAP38 in triggering migraine-like attacks.

Main Methods:

• A double-blind, three-way cross-over pilot study involving six MO patients.
• Intravenous infusion of PACAP38 at 4, 6, and 8 pmol/kg/min over 20 minutes.
• Recording of headache and migraine characteristics over a 13-hour period.

Main Results:

• Migraine-like attacks were induced in 1/6 patients at 4 pmol/kg/min, 2/6 at 6 pmol/kg/min, and 3/6 at 8 pmol/kg/min.
• All patients reported head pain at 8 pmol/kg/min, and five out of six reported head pain at 4 and 6 pmol/kg/min.
• An exploratory analysis indicated a significant difference in headache intensity between 4 pmol/kg/min and 8 pmol/kg/min PACAP38.

Conclusions:

• A trend suggesting a dose-response relationship between PACAP38 dose and migraine incidence was observed.
• The findings support the hypothesis that higher PACAP38 doses are more effective in inducing migraine-like attacks.
• 10 pmol/kg/min PACAP38 remains the suggested optimal dose for reliably inducing migraine-like attacks in MO patients.