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Hypersensitivity to PACAP-38 in post-traumatic headache: a randomized clinical trial
Haidar M Al-Khazali1,2,3,4, Rune H Christensen1,2,3,4, David W Dodick4,5
1Harvard Medical School, Boston, MA 02115, USA.
Brain : a Journal of Neurology
|October 21, 2023
Summary
Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) infusion induced migraine-like headaches in 95% of participants with persistent post-traumatic headache (PTH). Targeting PACAP-38 may offer a new treatment for PTH.
Area of Science:
- Neuroscience
- Pharmacology
- Headache Medicine
Background:
- Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) is implicated in migraine pathogenesis.
- Clinical similarities exist between post-traumatic headache (PTH) and migraine.
- PACAP-38 is a potential novel drug target for headache disorders.
Purpose of the Study:
- To investigate the role of PACAP-38 in the pathogenesis of persistent PTH.
- To determine if PACAP-38 can induce migraine-like headaches in individuals with PTH.
Main Methods:
- A randomized, double-blind, placebo-controlled, two-way crossover trial was conducted.
- Adult participants with persistent PTH received intravenous infusions of PACAP-38 or placebo.
- Headache incidence and intensity were monitored for 12 hours post-infusion.
Main Results:
- 95% of participants developed migraine-like headaches after PACAP-38 infusion, compared to 10% after placebo (P < 0.001).
- Headache intensity, measured by AUC, was significantly higher following PACAP-38 infusion (P < 0.001).
- The study enrolled 21 participants (76% female, mean age 35.2 years).
Conclusions:
- PACAP-38 is a potent inducer of migraine-like headaches in individuals with persistent PTH.
- Targeting PACAP-38 signaling presents a promising therapeutic strategy for PTH treatment.
