Journal
FRONTIERS IN PHARMACOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.01078
Keywords
pain; opioid; opioid receptor; heterodimer; side effect
Categories
Funding
- National Natural Science Foundation of China [81870874]
- Natural Science Foundation of Jiangsu Province, China [BK20170004, 2015-JY-029]
- Jiangsu Key Laboratory of Neuropsychiatric Diseases [BM2013003]
- Social Development Special Fund of Kunshan [KS1931]
- Clinical and basic research of encephalopathy [KYC004]
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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 receptorsin vitroandin 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.
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