biostudies-literatureKibaly CNIDA NIH HHSNational Institutes of Health153-168https://www.ebi.ac.uk/biostudies/studies/S-EPMC5392433biostudies-literatureUnknown119The development of tolerance to morphine, one of the most potent analgesics, in the management of chronic pain is a significant clinical problem and its mechanisms are poorly understood. Morphine exerts its pharmacological effects via the μ-opioid receptor (MOR). Tolerance is highly connected to G-protein-coupled receptors (GPCR) phosphorylation and desensitization increase. Because morphine desensitization previously has been shown to be MOR phosphorylation- and ß-arrestin2-independent (in contrast to agonists such as fentanyl), we examined the contribution of phosphorylation of the entire C-terminus to the development of antinociceptive tolerance to the partial (morphine) and full (fentanyl) MOR agonists in vivo. In MOR knockout (MORKO) mice, we delivered via lentivirus the genes encodinPharmacological researchSpinal or supraspinal phosphorylation deficiency at the MOR C-terminus does not affect morphine tolerance in vivo.PMC5392433DA031442P50 DA011806R01 DA031442DA011806Kibaly CLoh HHLin HYLaw PYfalseSpinal or supraspinal phosphorylation deficiency at the MOR C-terminus does not affect morphine tolerance in vivo.The development of tolerance to morphine, one of the most potent analgesics, in the management of chronic pain is a significant clinical problem and its mechanisms are poorly understood. Morphine exerts its pharmacological effects via the μ-opioid receptor (MOR). Tolerance is highly connected to G-protein-coupled receptors (GPCR) phosphorylation and desensitization increase. Because morphine desensitization previously has been shown to be MOR phosphorylation- and ß-arrestin2-independent (in contrast to agonists such as fentanyl), we examined the contribution of phosphorylation of the entire C-terminus to the development of antinociceptive tolerance to the partial (morphine) and full (fentanyl) MOR agonists in vivo. In MOR knockout (MORKO) mice, we delivered via lentivirus the genes encodin2017-01-01T00:00:00Z2017 May2025-04-04T02:12:05.683Z2019-03-26T23:33:50ZS-EPMC53924332817912310.1016/j.phrs.2017.01.033