Opioid receptor desensitization: mechanisms and its link to tolerance

Front Pharmacol. 2014 Dec 18:5:280. doi: 10.3389/fphar.2014.00280. eCollection 2014.


Opioid receptors (OR) are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization, and post-endocytic fate of the receptor.

Keywords: biased signaling; desensitization; opioid receptors; receptor trafficking; tolerance mechanisms.

Publication types

  • Review