Inhibition of Pain Signal Conduction in Dorsal Root Ganglion Neurons by Optogenetic Technique Mediated with Upconversion Nanoparticles

Traditional analgesic strategies not only have limited efficacy but also tend to cause side effects such as drug dependence and gastrointestinal tract damage. As a popular nonpharmacological neural modulation approach, optogenetic technology has seen increasingly in-depth research in the field of pain regulation. The dorsal root ganglion (DRG), a crucial relay station for pain information transmission, serves as a key target for pain regulation. Optogenetic technology holds broad prospects for pain regulation at the DRG. However, the application of traditional optogenetic technology in pain regulation at the DRG is restricted due to issues such as limited light penetration depth, trauma caused by fiber-optic implantation, and difficulty in fixing the optical fibers in the DRG region. This study developed a wireless optogenetic system based on upconversion nanoparticles (UCNPs). UCNPs can effectively convert near-infrared light into visible light in the DRG and activate neurons transfected with photosensitive proteins. The whole system does not require optical fiber implantation. The results demonstrated that UCNPs emitted under near-infrared light excitation could effectively activate ChR2 expressed in the DRG to induce excitatory currents, or activate SwiChRca and inhibit the generation of abnormal action potentials in the patch-clamp experiment. In behavioral experiments, near-infrared-triggered blue emission from UCNPs prolonged paw withdrawal latency in mice with inflammatory pain, indicating elevated pain threshold and analgesic efficacy. Meanwhile, the experimental animals were allowed to move freely, thereby enabling sophisticated behavioral assessments and facilitating mechanistic investigations and precision pain management.