Selective Activation of the Adrenomedullin Receptors in Migraine

Adrenomedullin is an endogenous neuropeptide structurally related to CGRP that can activate both the adrenomedullin receptor and, to a lesser extent, the CGRP receptor. Prior human provocation studies have shown that administration of adrenomedullin can elicit migraine attacks in people with migraine. Because adrenomedullin lacks receptor selectivity, physiological responses observed after its administration might represent a composite of adrenomedullin-receptor activation and potential off-target activation of the CGRP receptor. The extent to which selective activation of the adrenomedullin receptor alone can provoke migraine-relevant responses remains unknown. To isolate adrenomedullin receptor-mediated effects, participants will receive the monoclonal antibody erenumab prior to adrenomedullin administration in order to block CGRP receptor activation. This study therefore aims to determine whether selective activation of adrenomedullin receptors - isolated from confounding CGRP receptor activation - can induce migraine-relevant physiological responses.