HEADACHE: Edited by Peter J. GoadsbyDelta-opioid receptors as targets for migraine therapyCharles, Andrew; Pradhan, Amynah A.Author Information aUCLA Goldberg Migraine Program, David Geffen School of Medicine at UCLA, Los Angeles, California bDepartment of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA Correspondence to Andrew Charles, UCLA Goldberg Migraine Program, David Geffen School of Medicine at UCLA, 635 Charles Young Drive, Los Angeles, CA 90095, USA. Tel: +1 310 794 1870; e-mail: [email protected] Current Opinion in Neurology: June 2016 - Volume 29 - Issue 3 - p 314-319 doi: 10.1097/WCO.0000000000000311 Buy Metrics Abstract Purpose of review The purpose of this review is to contrast the properties of the δ-opioid receptor with those of the μ-opioid receptor, which is the primary target of most currently available opioid analgesics. We also discuss preclinical evidence that indicates the potential efficacy of δ-opioid receptor agonists as migraine therapy. Recent findings The use of currently available opioid analgesics is highly problematic for patients with migraine. Delta-opioid receptors have key differences from μ receptors; these differences make the δ receptor an attractive therapeutic target for migraine. Delta-opioid receptors are expressed in both the peripheral and central nervous system in anatomical regions and cell types that are believed to play a role in migraine. Delta-receptor agonists have also shown promising effects in multiple migraine models, including nitroglycerin evoked hyperalgesia and conditioned place aversion, and cortical spreading depression. Evidence from animal models indicates that activation of δ receptors is less likely to cause tolerance and dependence, and less likely to cause hyperalgesia. In addition, δ receptors may have antidepressant and anxiolytic properties that are distinct from those of μ receptors. In human studies investigating other conditions, δ-receptor agonists have been generally safe and well tolerated. Summary Delta-opioid receptor agonists have promising potential as acute and/or preventive migraine therapies, without the problems associated with currently used opioid analgesics. Copyright © 2016 Wolters Kluwer Health, Inc. All rights resereved.