Abstract Background Managing moderate-to-severe postoperative pain remains a major clinical challenge. Traditional opioids are constrained by dose-limiting opioid-related adverse events (ORAEs), including respiratory depression, nausea, vomiting, and constipation. Objective Biased μ-opioid receptor (MOR) agonists were developed to preferentially activate G-protein signaling, which mediates analgesia, while attenuating β-arrestin-2 recruitment, which has been associated with adverse effects.
