Fig. 1.

Overview of the “from Beside to Bench” strategy: Nalfurafine, the only KOR agonist in clinical use, has antipruritic effect without dysphoric effects and a very low rate of hallucinations, two side effects commonly associated with other KOR agonists. To investigate the biochemical mechanism, we established a mouse model to compare the effect of nalfurafine and U50,488H, a prototypic KOR agonist. This animal model enabled us to conduct mass spectrometry-based systems biology analysis. The insights obtained allowed us to generate and test hypothesis using behavioral tests, biochemical and pharmacological assays. This integrated strategy allowed us to bypass the in vitro model to generate insights that could impact on future drug discovery