LAUSR

modulating PACAP-38-induced hypersensitivity between the RAMP1 deficient and wild-type mice. Furthermore, the humanized monoclonal CGRP antibody (ALD405) did not prevent PACAP-38-induced hypersensitivity in wild-type mice. In addition, the study found that the TRPA1 channel was not involved in PACAP-38-induced hypersensitivity. Interestingly, GTN hypersensitivity is dependent on RAMP1 and TRPA1. Finally, the study showed that a non-selective K ATP channel inhibitor glibenclamide partially inhibited PACAP-38-induced hypersensitivity. These results contrast with human data showing that glibenclamide did not attenuate PACAP-38-induced headache and haemodynamic changes in healthy volunteers, 9 but the potency of glibenclamide on the rele-vant subtype K ATP channel is probably too small in humans. Together, both studies provide new data supporting the possible use of delta opioid agonists and anti-PACAP drugs in migraine treatment. More studies in humans are needed to assess the safety and risk of addiction to delta opioids. Monoclonal PAC 1 receptor antibody failed in a proof-of-concept study for migraine prevention, 10 and two ongoing randomized clinical trials on the efficacy, safety and tolerability of monoclonal antibodies designed to target PACAP (ClinicalTrials.gov NCT04498910; ClinicalTrials.gov Identifier: NCT05133323) will reveal whether targeting PACAP-signalling is effective for migraine prevention.