Role of β-Arrestin 2 in the antinociceptive and side effect profile of morphine and the novel mu opioid receptor agonists, kurkinorin and kurkinol.

ABSTRACT: The development of safer mu opioid receptor (MOR) agonists with reduced side effects is a key focus of pain research. Some studies have suggested that MOR agonists with reduced β-arrestin 2 (βArr2) signaling (i.e. G-protein biased agonists) may have greater therapeutic windows. However, there have been a several conflicting reports, and it is not clear what role, if any, βArr2 signaling plays in MOR-mediated analgesia, tolerance, or side effects. Therefore, we used βArr2 knockout mice to systematically investigate the causal role of βArr2 signaling in antinociception, antinociceptive tolerance, respiratory depression, constipation, and reward induced by morphine and the two novel MOR agonists, kurkinorin and kurkinol. Kurkinorin and kurkinol exhibited potent antinociceptive effects that we

SUBMITTER: van de Wetering R 

PROVIDER: S-EPMC12518651 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature