Contrary to other migraine-inducing substances like GTN, cilostazol, and levcromakalim, PACAP-38-induced hypersensitivity worked only partially through KATP channel inhibition. Conclusion: These findings establish the PACAP-38 pathway as distinct from the migraine provoking agents CGRP and GTN. PACAP antagonism may therefore be a novel therapeutic target, of particular interest in patients unresponsive to CGRP antagonists. The gene discussed is ADCYAP1; the disease is migraine disorder.