Wireless, battery-free, remote photoactivation of caged-morphine for photopharmacological pain modulation without side effects

Abstract

Chronic pain severely impairs physical, psychological, and cognitive functions. While opioid-based therapies can be effective, they are limited by tolerance, dependence, and adverse side effects, highlighting the need for safer alternatives. Recent advances in photopharmacology allow precise modulation of pain-related neuronal circuits, offering improved control and effectiveness. For delivery of light, fully implantable, wireless, battery-free optical systems in miniaturized forms offer attractive options relative to alternatives that use conventional bulk hardware and fiber optic tethers. This work presents a technology of this type, based on microscale light-emitting diodes (μ-ILEDs) and near-field communication (NFC) protocols, and optimized to activate photocaged morphine (pc-Mor) in targeted regions of the spinal cord. The unique flexible, lightweight designs ensure stable, minimally invasive operation in small animal model behavioral studies, with efficient power consumption and minimized thermal load on fragile tissues. Experimental results demonstrate effective pain suppression and reduced opioid-related side effects in an animal model of pain, thereby establishing this platform as a promising solution for chronic pain management.