The three opioid receptors, mu, delta and kappa all mediate analgesia, and knockout mice with opioid receptor deletion have
proven unique tools to investigate in vivo opioid pharmacology. Since a few years, a number of new mouse lines have been engineered,
with several distinct mutations of the mu receptor, to assess the role of specific amino acid residues or peptidic sequences of this receptor
in analgesia and tolerance. The analysis of analgesia in mice deleted in kappa receptor and triple mu/delta/kappa receptor knockout mice
have provided advances in opioid-induced analgesia. Also, the global and conditional deletion of the delta receptor in peripheral nociceptive
neurons has revealed the participation of the targeted receptors in opioid-induced analgesia. Another approach for the study of opioid
receptors is the visualization of these receptors in vivo, by engineering of knock-in mice with fluorescently tagged receptors. A mouse
line with a fluorescent delta receptor has allowed live imaging of this receptor in behavioral paradigms and first studies on ligand-biased
agonism at this receptor in vivo. The studies with mutant mouse lines for opioid receptors, combined with novel molecular and pharmacological
approaches, will allow to develop novel strategies for opioid-based analgesia. This review summarizes the different genetically
modified mouse lines for opioid receptors as well as the data and concepts inferred from analgesia results on these mutant mouse lines.
Keywords: Opioid receptors, mu, delta, kappa, knockout, conditional knockout, mouse mutant, analgesia.
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