AUTHOR=Zhang Li, Zhang Jiang-Tao, Hang Lihua, Liu Tong TITLE=Mu Opioid Receptor Heterodimers Emerge as Novel Therapeutic Targets: Recent Progress and Future Perspective JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/articles/10.3389/fphar.2020.01078 DOI=10.3389/fphar.2020.01078 ISSN=1663-9812 ABSTRACT=Opioids are the most effective analgesics used in the clinical management of cancer pain or non-cancer pain. However, chronic opioids therapy can cause many side effects including respiratory depression, nausea, sedation, itch, constipation, analgesic tolerance, hyperalgesia, high addictive potential, and abuse liability. Opioids exert their effects through binding to the opioid receptors belonging to the G-protein coupled receptors (GPCRs) family, including mu opioid receptor (MOR), delta opioid receptor (DOR), and kappa opioid receptor (KOR). Among them, MOR is essential for opioid-induced analgesia and also responsible for adverse effects of opioids. Importantly, MOR can form heterodimers with other opioid receptors and non-opioid receptors in vitro and in vivo, and has distinct pharmacological properties, different binding affinities for ligands, downstream signaling, and receptor trafficking. This mini review summarized recent progress on the function of Mu opioid receptor heterodimers, and we proposed that targeting mu opioid receptor heterodimers may represent an opportunity to develop new therapeutics, especially for chronic pain treatment.