Therapeutic potential of opioid receptor heteromers in chronic pain and associated comorbidities.

Chronic pain affects 20% to 45% of the global population and is often associated with the development of anxio-depressive disorders. Treatment of this debilitating condition remains particularly challenging with opioids prescribed to alleviate moderate to severe pain. However, despite strong antinociceptive properties, numerous adverse effects limit opioid use in the clinic. Moreover, opioid misuse and abuse have become a major health concern worldwide. This prompted efforts to design original strategies that would efficiently and safely relieve pain. Targeting of opioid receptor heteromers is one of these. This review summarizes our current knowledge on the role of heteromers involving opioid receptors in the context of chronic pain and anxio-depressive comorbidities. It also examines how heteromerization in native tissue affects ligand binding, receptor signalling and trafficking properties. Finally, the therapeutic potential of ligands designed to specifically target opioid receptor heteromers is considered. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.