Reprogramming pain signaling through photopharmacology

Pain remains a major clinical challenge because current analgesics lack spatiotemporal precision and frequently induce systemic adverse effects, tolerance, and dependence. Recent advances in photopharmacology have enabled reversible optical control of ion channels, G protein-coupled receptors, and neural circuits involved in nociceptive processing, providing new opportunities for precision analgesia. Progress in photoswitches, photocaged ligands, wireless optoelectronic systems, and nanodelivery platforms has substantially improved the in vivo applicability of light-responsive therapeutics. These developments have transformed photopharmacology from a mechanistic research tool into a potential translational strategy for pain treatment. In this review, we discuss how photopharmacological approaches are reshaping the investigation of peripheral and central pain signaling, highlight emerging light-controlled analgesics, and outline future directions toward clinically translatable, nonaddictive, and personalized pain therapeutics.