A phototriggerable system whereby patients could repeatedly and non-invasively control the timing and dosage of local anesthesia according to their needs would be beneficial for perioperative pain and perhaps obviate the need for oral narcotics. However, clinical application of phototriggerable systems have been limited by concerns over phototoxicity of lasers and limited tissue penetration of light. To address these limitations, we increased the devices’ effective sensitivity to light by co-delivering a second compound, dexmedetomidine, that potentiates the effect of delivered local anesthetics. The concurrent release of dexmedetomidine enhanced the efficacy of released local anesthetics, greatly increasing the number of triggerable nerve blocks (up to nine triggerable events upon a single injection) and reducing the irradiance needed to induce nerve block by 94%. The intensity and duration of on-demand analgesia could be adjusted by varying the intensity and duration of irradiance, which could not only be delivered by lasers, but also by light-emitting diodes, which are less expensive, safer, and more portable.