Advances in the Development and Imaging Applications of Fluorescent Probes for Opioid Receptors.

Traditional opioid analgesics remain the "gold standard" for managing moderate-to-severe pain. There is an urgent need for advanced pharmacological tools to facilitate the discovery of safer and more effective analgesics. Fluorescent probe technology offers high sensitivity and a favorable signal-to-noise ratio, making it well-suited for visualizing cellular signaling events as well as ligand-receptor interactions both in vitro and in vivo. This perspective provides a systematic overview of advances in fluorescent probes targeting the four opioid receptor subtypes (μ-, κ-, δ-opioid and nociceptin/orphanin FQ receptor), focusing on ligand scaffold and fluorophore designs, imaging applications, and technical advantages. We also discuss current challenges and future directions. Overall, this perspective provides a comprehensive reference for research and applications of opioid receptor fluorescent probes, thereby facilitating their extensive utilization in elucidating opioid analgesic mechanisms and side effects.