[Opioid tolerance: what if it was just a question of receptor internalization?].

Abstract

Despite side effects which appear upon chronic administration of opioid agonists, these drugs remain widely used and effective for pain relief. Among these side effects, tolerance is the major factor limiting the effectiveness of these drugs. Desensitization, defined by a decrease of opioid receptor transduction, would be a crucial step in the development of tolerance. Molecular mechanisms of opioid receptor desensitization have been extensively studied on cellular models and have been found to involve various proteins and different steps such as receptor phosphorylation, internalization, and recycling or degradation into intracellular compartments. In the present review, we discuss the role of opioid receptor internalization and sorting in desensitization and tolerance processes